Severe acute respiratory syndrome-coronavirus infection in aged nonhuman primates is associated with modulated pulmonary and systemic immune responses
Identifieur interne : 000662 ( Pmc/Curation ); précédent : 000661; suivant : 000663Severe acute respiratory syndrome-coronavirus infection in aged nonhuman primates is associated with modulated pulmonary and systemic immune responses
Auteurs : Candice C. Clay [Mexique, États-Unis] ; Nathan Donart [Mexique] ; Ndingsa Fomukong [Mexique] ; Jennifer B. Knight [Mexique] ; Katie Overheim [Mexique] ; Jennifer Tipper [Mexique] ; Jesse Van Westrienen [Mexique] ; Fletcher Hahn [Mexique] ; Kevin S. Harrod [Mexique]Source :
- Immunity & Ageing : I & A [ 1742-4933 ] ; 2014.
Abstract
Many respiratory viruses disproportionately impact the elderly. Likewise, advanced age correlated with more adverse disease outcomes following severe acute respiratory syndrome coronavirus (SARS-CoV) infection in humans. We used an aged African green monkey SARS-CoV infection model to better understand age-related mechanisms of increased susceptibility to viral respiratory infections. Nonhuman primates are critical translational models for such research given their similarities to humans in immune-ageing as well as lung structure.
Significant age- and infection-dependent differences were observed in both systemic and mucosal immune compartments. Peripheral lymphocytes, specifically CD8 T and B cells were significantly lower in aged monkeys pre- and post- SARS-CoV infection, while neutrophil and monocyte numbers were not impacted by age or infection status. Serum proinflammatory cytokines were similar in both age groups, whereas significantly lower levels of IL-1beta, IL-18, IL-6, IL-12 and IL-15 were detected in the lungs of SARS-CoV-infected aged monkeys at either 5 or 10 days post infection. Total lung leukocyte numbers and relative frequency of CD8 T cells, B cells, macrophages and dendritic cells were greatly reduced in the aged host during SARS-CoV infection, despite high levels of chemoattractants for many of these cells in the aged lung. Dendritic cells and monocytes/macrophages showed age-dependent differences in activation and chemokine receptor profiles, while the CD8 T cell and B cell responses were significantly reduced in the aged host. In examination of viral titers, significantly higher levels of SARS-CoV were detected in the nasal swabs early, at day 1 post infection, in aged as compared to juvenile monkeys, but virus levels were only slightly higher in aged animals by day 3. Although there was a trend of higher titers in respiratory tissues at day 5 post infection, this did not reach statistical significance and virus was cleared from all animals by day 10, regardless of age.
This study provides unique insight into how several parameters of the systemic and mucosal immune response to SARS-CoV infection are significantly modulated by age. These immune differences may contribute to deficient immune function and the observed trend of higher SARS-CoV replication in aged nonhuman primates.
Url:
DOI: 10.1186/1742-4933-11-4
PubMed: 24642138
PubMed Central: 3999990
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<wicri:regionArea>California National Primate Research Center, University of California, Davis, CA</wicri:regionArea>
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<author><name sortKey="Donart, Nathan" sort="Donart, Nathan" uniqKey="Donart N" first="Nathan" last="Donart">Nathan Donart</name>
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<author><name sortKey="Harrod, Kevin S" sort="Harrod, Kevin S" uniqKey="Harrod K" first="Kevin S" last="Harrod">Kevin S. Harrod</name>
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<series><title level="j">Immunity & Ageing : I & A</title>
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<front><div type="abstract" xml:lang="en"><sec><title>Background</title>
<p>Many respiratory viruses disproportionately impact the elderly. Likewise, advanced age correlated with more adverse disease outcomes following severe acute respiratory syndrome coronavirus (SARS-CoV) infection in humans. We used an aged African green monkey SARS-CoV infection model to better understand age-related mechanisms of increased susceptibility to viral respiratory infections. Nonhuman primates are critical translational models for such research given their similarities to humans in immune-ageing as well as lung structure.</p>
</sec>
<sec><title>Results</title>
<p>Significant age- and infection-dependent differences were observed in both systemic and mucosal immune compartments. Peripheral lymphocytes, specifically CD8 T and B cells were significantly lower in aged monkeys pre- and post- SARS-CoV infection, while neutrophil and monocyte numbers were not impacted by age or infection status. Serum proinflammatory cytokines were similar in both age groups, whereas significantly lower levels of IL-1beta, IL-18, IL-6, IL-12 and IL-15 were detected in the lungs of SARS-CoV-infected aged monkeys at either 5 or 10 days post infection. Total lung leukocyte numbers and relative frequency of CD8 T cells, B cells, macrophages and dendritic cells were greatly reduced in the aged host during SARS-CoV infection, despite high levels of chemoattractants for many of these cells in the aged lung. Dendritic cells and monocytes/macrophages showed age-dependent differences in activation and chemokine receptor profiles, while the CD8 T cell and B cell responses were significantly reduced in the aged host. In examination of viral titers, significantly higher levels of SARS-CoV were detected in the nasal swabs early, at day 1 post infection, in aged as compared to juvenile monkeys, but virus levels were only slightly higher in aged animals by day 3. Although there was a trend of higher titers in respiratory tissues at day 5 post infection, this did not reach statistical significance and virus was cleared from all animals by day 10, regardless of age.</p>
</sec>
<sec><title>Conclusions</title>
<p>This study provides unique insight into how several parameters of the systemic and mucosal immune response to SARS-CoV infection are significantly modulated by age. These immune differences may contribute to deficient immune function and the observed trend of higher SARS-CoV replication in aged nonhuman primates.</p>
</sec>
</div>
</front>
<back><div1 type="bibliography"><listBibl><biblStruct><analytic><author><name sortKey="Salvioli, S" uniqKey="Salvioli S">S Salvioli</name>
</author>
<author><name sortKey="Capri, M" uniqKey="Capri M">M Capri</name>
</author>
<author><name sortKey="Valensin, S" uniqKey="Valensin S">S Valensin</name>
</author>
<author><name sortKey="Tieri, P" uniqKey="Tieri P">P Tieri</name>
</author>
<author><name sortKey="Monti, D" uniqKey="Monti D">D Monti</name>
</author>
<author><name sortKey="Ottaviani, E" uniqKey="Ottaviani E">E Ottaviani</name>
</author>
<author><name sortKey="Franceschi, C" uniqKey="Franceschi C">C Franceschi</name>
</author>
</analytic>
</biblStruct>
<biblStruct><analytic><author><name sortKey="Pawelec, G" uniqKey="Pawelec G">G Pawelec</name>
</author>
</analytic>
</biblStruct>
<biblStruct><analytic><author><name sortKey="Globerson, A" uniqKey="Globerson A">A Globerson</name>
</author>
<author><name sortKey="Effros, Rb" uniqKey="Effros R">RB Effros</name>
</author>
</analytic>
</biblStruct>
<biblStruct><analytic><author><name sortKey="Panda, A" uniqKey="Panda A">A Panda</name>
</author>
<author><name sortKey="Arjona, A" uniqKey="Arjona A">A Arjona</name>
</author>
<author><name sortKey="Sapey, E" uniqKey="Sapey E">E Sapey</name>
</author>
<author><name sortKey="Bai, F" uniqKey="Bai F">F Bai</name>
</author>
<author><name sortKey="Fikrig, E" uniqKey="Fikrig E">E Fikrig</name>
</author>
<author><name sortKey="Montgomery, Rr" uniqKey="Montgomery R">RR Montgomery</name>
</author>
<author><name sortKey="Lord, Jm" uniqKey="Lord J">JM Lord</name>
</author>
<author><name sortKey="Shaw, Ac" uniqKey="Shaw A">AC Shaw</name>
</author>
</analytic>
</biblStruct>
<biblStruct><analytic><author><name sortKey="Asquith, M" uniqKey="Asquith M">M Asquith</name>
</author>
<author><name sortKey="Haberthur, K" uniqKey="Haberthur K">K Haberthur</name>
</author>
<author><name sortKey="Brown, M" uniqKey="Brown M">M Brown</name>
</author>
<author><name sortKey="Engelmann, F" uniqKey="Engelmann F">F Engelmann</name>
</author>
<author><name sortKey="Murphy, A" uniqKey="Murphy A">A Murphy</name>
</author>
<author><name sortKey="Al Mahdi, Z" uniqKey="Al Mahdi Z">Z Al-Mahdi</name>
</author>
<author><name sortKey="Messaoudi, I" uniqKey="Messaoudi I">I Messaoudi</name>
</author>
</analytic>
</biblStruct>
<biblStruct><analytic><author><name sortKey="Aw, D" uniqKey="Aw D">D Aw</name>
</author>
<author><name sortKey="Silva, Ab" uniqKey="Silva A">AB Silva</name>
</author>
<author><name sortKey="Palmer, Db" uniqKey="Palmer D">DB Palmer</name>
</author>
</analytic>
</biblStruct>
<biblStruct><analytic><author><name sortKey="Aspinall, R" uniqKey="Aspinall R">R Aspinall</name>
</author>
<author><name sortKey="Del Giudice, G" uniqKey="Del Giudice G">G Del Giudice</name>
</author>
<author><name sortKey="Effros, Rb" uniqKey="Effros R">RB Effros</name>
</author>
<author><name sortKey="Grubeck Loebenstein, B" uniqKey="Grubeck Loebenstein B">B Grubeck-Loebenstein</name>
</author>
<author><name sortKey="Sambhara, S" uniqKey="Sambhara S">S Sambhara</name>
</author>
</analytic>
</biblStruct>
<biblStruct><analytic><author><name sortKey="Coe, Cl" uniqKey="Coe C">CL Coe</name>
</author>
<author><name sortKey="Lubach, Gr" uniqKey="Lubach G">GR Lubach</name>
</author>
<author><name sortKey="Kinnard, J" uniqKey="Kinnard J">J Kinnard</name>
</author>
</analytic>
</biblStruct>
<biblStruct><analytic><author><name sortKey="Fujihashi, K" uniqKey="Fujihashi K">K Fujihashi</name>
</author>
<author><name sortKey="Kiyono, H" uniqKey="Kiyono H">H Kiyono</name>
</author>
</analytic>
</biblStruct>
<biblStruct><analytic><author><name sortKey="Koga, T" uniqKey="Koga T">T Koga</name>
</author>
<author><name sortKey="Mcghee, Jr" uniqKey="Mcghee J">JR McGhee</name>
</author>
<author><name sortKey="Kato, H" uniqKey="Kato H">H Kato</name>
</author>
<author><name sortKey="Kato, R" uniqKey="Kato R">R Kato</name>
</author>
<author><name sortKey="Kiyono, H" uniqKey="Kiyono H">H Kiyono</name>
</author>
<author><name sortKey="Fujihashi, K" uniqKey="Fujihashi K">K Fujihashi</name>
</author>
</analytic>
</biblStruct>
<biblStruct><analytic><author><name sortKey="Sprung, J" uniqKey="Sprung J">J Sprung</name>
</author>
<author><name sortKey="Gajic, O" uniqKey="Gajic O">O Gajic</name>
</author>
<author><name sortKey="Warner, Do" uniqKey="Warner D">DO Warner</name>
</author>
</analytic>
</biblStruct>
<biblStruct><analytic><author><name sortKey="Rossi, A" uniqKey="Rossi A">A Rossi</name>
</author>
<author><name sortKey="Ganassini, A" uniqKey="Ganassini A">A Ganassini</name>
</author>
<author><name sortKey="Tantucci, C" uniqKey="Tantucci C">C Tantucci</name>
</author>
<author><name sortKey="Grassi, V" uniqKey="Grassi V">V Grassi</name>
</author>
</analytic>
</biblStruct>
<biblStruct><analytic><author><name sortKey="Herring, Mj" uniqKey="Herring M">MJ Herring</name>
</author>
<author><name sortKey="Avdalovic, Mv" uniqKey="Avdalovic M">MV Avdalovic</name>
</author>
<author><name sortKey="Quesenberry, Cl" uniqKey="Quesenberry C">CL Quesenberry</name>
</author>
<author><name sortKey="Putney, Lf" uniqKey="Putney L">LF Putney</name>
</author>
<author><name sortKey="Tyler, Nk" uniqKey="Tyler N">NK Tyler</name>
</author>
<author><name sortKey="Ventimiglia, Ff" uniqKey="Ventimiglia F">FF Ventimiglia</name>
</author>
<author><name sortKey="St George, Ja" uniqKey="St George J">JA St George</name>
</author>
<author><name sortKey="Hyde, Dm" uniqKey="Hyde D">DM Hyde</name>
</author>
</analytic>
</biblStruct>
<biblStruct><analytic><author><name sortKey="Chan Yeung, M" uniqKey="Chan Yeung M">M Chan-Yeung</name>
</author>
<author><name sortKey="Xu, Rh" uniqKey="Xu R">RH Xu</name>
</author>
</analytic>
</biblStruct>
<biblStruct><analytic><author><name sortKey="Gu, J" uniqKey="Gu J">J Gu</name>
</author>
<author><name sortKey="Korteweg, C" uniqKey="Korteweg C">C Korteweg</name>
</author>
</analytic>
</biblStruct>
<biblStruct><analytic><author><name sortKey="Chen, J" uniqKey="Chen J">J Chen</name>
</author>
<author><name sortKey="Subbarao, K" uniqKey="Subbarao K">K Subbarao</name>
</author>
</analytic>
</biblStruct>
<biblStruct><analytic><author><name sortKey="Chan, Jw" uniqKey="Chan J">JW Chan</name>
</author>
<author><name sortKey="Ng, Ck" uniqKey="Ng C">CK Ng</name>
</author>
<author><name sortKey="Chan, Yh" uniqKey="Chan Y">YH Chan</name>
</author>
<author><name sortKey="Mok, Ty" uniqKey="Mok T">TY Mok</name>
</author>
<author><name sortKey="Lee, S" uniqKey="Lee S">S Lee</name>
</author>
<author><name sortKey="Chu, Sy" uniqKey="Chu S">SY Chu</name>
</author>
<author><name sortKey="Law, Wl" uniqKey="Law W">WL Law</name>
</author>
<author><name sortKey="Lee, Mp" uniqKey="Lee M">MP Lee</name>
</author>
<author><name sortKey="Li, Pc" uniqKey="Li P">PC Li</name>
</author>
</analytic>
</biblStruct>
<biblStruct><analytic><author><name sortKey="Booth, Cm" uniqKey="Booth C">CM Booth</name>
</author>
<author><name sortKey="Matukas, Lm" uniqKey="Matukas L">LM Matukas</name>
</author>
<author><name sortKey="Tomlinson, Ga" uniqKey="Tomlinson G">GA Tomlinson</name>
</author>
<author><name sortKey="Rachlis, Ar" uniqKey="Rachlis A">AR Rachlis</name>
</author>
<author><name sortKey="Rose, Db" uniqKey="Rose D">DB Rose</name>
</author>
<author><name sortKey="Dwosh, Ha" uniqKey="Dwosh H">HA Dwosh</name>
</author>
<author><name sortKey="Walmsley, Sl" uniqKey="Walmsley S">SL Walmsley</name>
</author>
<author><name sortKey="Mazzulli, T" uniqKey="Mazzulli T">T Mazzulli</name>
</author>
<author><name sortKey="Avendano, M" uniqKey="Avendano M">M Avendano</name>
</author>
<author><name sortKey="Derkach, P" uniqKey="Derkach P">P Derkach</name>
</author>
<author><name sortKey="Ephtimios, Ie" uniqKey="Ephtimios I">IE Ephtimios</name>
</author>
<author><name sortKey="Kitai, I" uniqKey="Kitai I">I Kitai</name>
</author>
<author><name sortKey="Mederski, Bd" uniqKey="Mederski B">BD Mederski</name>
</author>
<author><name sortKey="Shadowitz, Sb" uniqKey="Shadowitz S">SB Shadowitz</name>
</author>
<author><name sortKey="Gold, Wl" uniqKey="Gold W">WL Gold</name>
</author>
<author><name sortKey="Hawryluck, La" uniqKey="Hawryluck L">LA Hawryluck</name>
</author>
<author><name sortKey="Rea, E" uniqKey="Rea E">E Rea</name>
</author>
<author><name sortKey="Chenkin, Js" uniqKey="Chenkin J">JS Chenkin</name>
</author>
<author><name sortKey="Cescon, Dw" uniqKey="Cescon D">DW Cescon</name>
</author>
<author><name sortKey="Poutanen, Sm" uniqKey="Poutanen S">SM Poutanen</name>
</author>
<author><name sortKey="Detsky, As" uniqKey="Detsky A">AS Detsky</name>
</author>
</analytic>
</biblStruct>
<biblStruct><analytic><author><name sortKey="Rockx, B" uniqKey="Rockx B">B Rockx</name>
</author>
<author><name sortKey="Baas, T" uniqKey="Baas T">T Baas</name>
</author>
<author><name sortKey="Zornetzer, Ga" uniqKey="Zornetzer G">GA Zornetzer</name>
</author>
<author><name sortKey="Haagmans, B" uniqKey="Haagmans B">B Haagmans</name>
</author>
<author><name sortKey="Sheahan, T" uniqKey="Sheahan T">T Sheahan</name>
</author>
<author><name sortKey="Frieman, M" uniqKey="Frieman M">M Frieman</name>
</author>
<author><name sortKey="Dyer, Md" uniqKey="Dyer M">MD Dyer</name>
</author>
<author><name sortKey="Teal, Th" uniqKey="Teal T">TH Teal</name>
</author>
<author><name sortKey="Proll, S" uniqKey="Proll S">S Proll</name>
</author>
<author><name sortKey="Van Den Brand, J" uniqKey="Van Den Brand J">J van den Brand</name>
</author>
<author><name sortKey="Baric, R" uniqKey="Baric R">R Baric</name>
</author>
<author><name sortKey="Katze, Mg" uniqKey="Katze M">MG Katze</name>
</author>
</analytic>
</biblStruct>
<biblStruct><analytic><author><name sortKey="Baas, T" uniqKey="Baas T">T Baas</name>
</author>
<author><name sortKey="Roberts, A" uniqKey="Roberts A">A Roberts</name>
</author>
<author><name sortKey="Teal, Th" uniqKey="Teal T">TH Teal</name>
</author>
<author><name sortKey="Vogel, L" uniqKey="Vogel L">L Vogel</name>
</author>
<author><name sortKey="Chen, J" uniqKey="Chen J">J Chen</name>
</author>
<author><name sortKey="Tumpey, Tm" uniqKey="Tumpey T">TM Tumpey</name>
</author>
<author><name sortKey="Katze, Mg" uniqKey="Katze M">MG Katze</name>
</author>
<author><name sortKey="Subbarao, K" uniqKey="Subbarao K">K Subbarao</name>
</author>
</analytic>
</biblStruct>
<biblStruct><analytic><author><name sortKey="Nagata, N" uniqKey="Nagata N">N Nagata</name>
</author>
<author><name sortKey="Iwata, N" uniqKey="Iwata N">N Iwata</name>
</author>
<author><name sortKey="Hasegawa, H" uniqKey="Hasegawa H">H Hasegawa</name>
</author>
<author><name sortKey="Fukushi, S" uniqKey="Fukushi S">S Fukushi</name>
</author>
<author><name sortKey="Harashima, A" uniqKey="Harashima A">A Harashima</name>
</author>
<author><name sortKey="Sato, Y" uniqKey="Sato Y">Y Sato</name>
</author>
<author><name sortKey="Saijo, M" uniqKey="Saijo M">M Saijo</name>
</author>
<author><name sortKey="Taguchi, F" uniqKey="Taguchi F">F Taguchi</name>
</author>
<author><name sortKey="Morikawa, S" uniqKey="Morikawa S">S Morikawa</name>
</author>
<author><name sortKey="Sata, T" uniqKey="Sata T">T Sata</name>
</author>
</analytic>
</biblStruct>
<biblStruct><analytic><author><name sortKey="Smits, Sl" uniqKey="Smits S">SL Smits</name>
</author>
<author><name sortKey="De Lang, A" uniqKey="De Lang A">A de Lang</name>
</author>
<author><name sortKey="Van Den Brand, Jm" uniqKey="Van Den Brand J">JM van den Brand</name>
</author>
<author><name sortKey="Leijten, Lm" uniqKey="Leijten L">LM Leijten</name>
</author>
<author><name sortKey="Van, Iwf" uniqKey="Van I">IWF van</name>
</author>
<author><name sortKey="Eijkemans, Mj" uniqKey="Eijkemans M">MJ Eijkemans</name>
</author>
<author><name sortKey="Van Amerongen, G" uniqKey="Van Amerongen G">G van Amerongen</name>
</author>
<author><name sortKey="Kuiken, T" uniqKey="Kuiken T">T Kuiken</name>
</author>
<author><name sortKey="Andeweg, Ac" uniqKey="Andeweg A">AC Andeweg</name>
</author>
<author><name sortKey="Osterhaus, Ad" uniqKey="Osterhaus A">AD Osterhaus</name>
</author>
<author><name sortKey="Haagmans, Bl" uniqKey="Haagmans B">BL Haagmans</name>
</author>
</analytic>
</biblStruct>
<biblStruct><analytic><author><name sortKey="Plopper, Cg" uniqKey="Plopper C">CG Plopper</name>
</author>
<author><name sortKey="Hyde, Dm" uniqKey="Hyde D">DM Hyde</name>
</author>
</analytic>
</biblStruct>
<biblStruct><analytic><author><name sortKey="Messaoudi, I" uniqKey="Messaoudi I">I Messaoudi</name>
</author>
<author><name sortKey="Estep, R" uniqKey="Estep R">R Estep</name>
</author>
<author><name sortKey="Robinson, B" uniqKey="Robinson B">B Robinson</name>
</author>
<author><name sortKey="Wong, Sw" uniqKey="Wong S">SW Wong</name>
</author>
</analytic>
</biblStruct>
<biblStruct><analytic><author><name sortKey="Didier, Es" uniqKey="Didier E">ES Didier</name>
</author>
<author><name sortKey="Sugimoto, C" uniqKey="Sugimoto C">C Sugimoto</name>
</author>
<author><name sortKey="Bowers, Lc" uniqKey="Bowers L">LC Bowers</name>
</author>
<author><name sortKey="Khan, Ia" uniqKey="Khan I">IA Khan</name>
</author>
<author><name sortKey="Kuroda, Mj" uniqKey="Kuroda M">MJ Kuroda</name>
</author>
</analytic>
</biblStruct>
<biblStruct><analytic><author><name sortKey="Roth, Gs" uniqKey="Roth G">GS Roth</name>
</author>
<author><name sortKey="Mattison, Ja" uniqKey="Mattison J">JA Mattison</name>
</author>
<author><name sortKey="Ottinger, Ma" uniqKey="Ottinger M">MA Ottinger</name>
</author>
<author><name sortKey="Chachich, Me" uniqKey="Chachich M">ME Chachich</name>
</author>
<author><name sortKey="Lane, Ma" uniqKey="Lane M">MA Lane</name>
</author>
<author><name sortKey="Ingram, Dk" uniqKey="Ingram D">DK Ingram</name>
</author>
</analytic>
</biblStruct>
<biblStruct><analytic><author><name sortKey="Lane, Ma" uniqKey="Lane M">MA Lane</name>
</author>
</analytic>
</biblStruct>
<biblStruct><analytic><author><name sortKey="Clay, C" uniqKey="Clay C">C Clay</name>
</author>
<author><name sortKey="Donart, N" uniqKey="Donart N">N Donart</name>
</author>
<author><name sortKey="Fomukong, N" uniqKey="Fomukong N">N Fomukong</name>
</author>
<author><name sortKey="Knight, Jb" uniqKey="Knight J">JB Knight</name>
</author>
<author><name sortKey="Lei, W" uniqKey="Lei W">W Lei</name>
</author>
<author><name sortKey="Price, L" uniqKey="Price L">L Price</name>
</author>
<author><name sortKey="Hahn, F" uniqKey="Hahn F">F Hahn</name>
</author>
<author><name sortKey="Van Westrienen, J" uniqKey="Van Westrienen J">J Van Westrienen</name>
</author>
<author><name sortKey="Harrod, Ks" uniqKey="Harrod K">KS Harrod</name>
</author>
</analytic>
</biblStruct>
<biblStruct><analytic><author><name sortKey="Olson, Ts" uniqKey="Olson T">TS Olson</name>
</author>
<author><name sortKey="Ley, K" uniqKey="Ley K">K Ley</name>
</author>
</analytic>
</biblStruct>
<biblStruct><analytic><author><name sortKey="Campbell, Dj" uniqKey="Campbell D">DJ Campbell</name>
</author>
<author><name sortKey="Kim, Ch" uniqKey="Kim C">CH Kim</name>
</author>
<author><name sortKey="Butcher, Ec" uniqKey="Butcher E">EC Butcher</name>
</author>
</analytic>
</biblStruct>
<biblStruct></biblStruct>
<biblStruct><analytic><author><name sortKey="Peiris, Js" uniqKey="Peiris J">JS Peiris</name>
</author>
<author><name sortKey="Guan, Y" uniqKey="Guan Y">Y Guan</name>
</author>
<author><name sortKey="Yuen, Ky" uniqKey="Yuen K">KY Yuen</name>
</author>
</analytic>
</biblStruct>
<biblStruct><analytic><author><name sortKey="Peiris, Js" uniqKey="Peiris J">JS Peiris</name>
</author>
<author><name sortKey="Chu, Cm" uniqKey="Chu C">CM Chu</name>
</author>
<author><name sortKey="Cheng, Vc" uniqKey="Cheng V">VC Cheng</name>
</author>
<author><name sortKey="Chan, Ks" uniqKey="Chan K">KS Chan</name>
</author>
<author><name sortKey="Hung, If" uniqKey="Hung I">IF Hung</name>
</author>
<author><name sortKey="Poon, Ll" uniqKey="Poon L">LL Poon</name>
</author>
<author><name sortKey="Law, Ki" uniqKey="Law K">KI Law</name>
</author>
<author><name sortKey="Tang, Bs" uniqKey="Tang B">BS Tang</name>
</author>
<author><name sortKey="Hon, Ty" uniqKey="Hon T">TY Hon</name>
</author>
<author><name sortKey="Chan, Cs" uniqKey="Chan C">CS Chan</name>
</author>
<author><name sortKey="Chan, Kh" uniqKey="Chan K">KH Chan</name>
</author>
<author><name sortKey="Ng, Js" uniqKey="Ng J">JS Ng</name>
</author>
<author><name sortKey="Zheng, Bj" uniqKey="Zheng B">BJ Zheng</name>
</author>
<author><name sortKey="Ng, Wl" uniqKey="Ng W">WL Ng</name>
</author>
<author><name sortKey="Lai, Rw" uniqKey="Lai R">RW Lai</name>
</author>
<author><name sortKey="Guan, Y" uniqKey="Guan Y">Y Guan</name>
</author>
<author><name sortKey="Yuen, Ky" uniqKey="Yuen K">KY Yuen</name>
</author>
</analytic>
</biblStruct>
<biblStruct><analytic><author><name sortKey="Cavalieri, Ta" uniqKey="Cavalieri T">TA Cavalieri</name>
</author>
<author><name sortKey="Chopra, A" uniqKey="Chopra A">A Chopra</name>
</author>
<author><name sortKey="Bryman, Pn" uniqKey="Bryman P">PN Bryman</name>
</author>
</analytic>
</biblStruct>
<biblStruct><analytic><author><name sortKey="Stout Delgado, Hw" uniqKey="Stout Delgado H">HW Stout-Delgado</name>
</author>
<author><name sortKey="Vaughan, Se" uniqKey="Vaughan S">SE Vaughan</name>
</author>
<author><name sortKey="Shirali, Ac" uniqKey="Shirali A">AC Shirali</name>
</author>
<author><name sortKey="Jaramillo, Rj" uniqKey="Jaramillo R">RJ Jaramillo</name>
</author>
<author><name sortKey="Harrod, Ks" uniqKey="Harrod K">KS Harrod</name>
</author>
</analytic>
</biblStruct>
<biblStruct><analytic><author><name sortKey="Chen, J" uniqKey="Chen J">J Chen</name>
</author>
<author><name sortKey="Lau, Yf" uniqKey="Lau Y">YF Lau</name>
</author>
<author><name sortKey="Lamirande, Ew" uniqKey="Lamirande E">EW Lamirande</name>
</author>
<author><name sortKey="Paddock, Cd" uniqKey="Paddock C">CD Paddock</name>
</author>
<author><name sortKey="Bartlett, Jh" uniqKey="Bartlett J">JH Bartlett</name>
</author>
<author><name sortKey="Zaki, Sr" uniqKey="Zaki S">SR Zaki</name>
</author>
<author><name sortKey="Subbarao, K" uniqKey="Subbarao K">K Subbarao</name>
</author>
</analytic>
</biblStruct>
<biblStruct><analytic><author><name sortKey="Nikolich Zugich, J" uniqKey="Nikolich Zugich J">J Nikolich-Zugich</name>
</author>
</analytic>
</biblStruct>
<biblStruct><analytic><author><name sortKey="Agrawal, A" uniqKey="Agrawal A">A Agrawal</name>
</author>
<author><name sortKey="Agrawal, S" uniqKey="Agrawal S">S Agrawal</name>
</author>
<author><name sortKey="Cao, Jn" uniqKey="Cao J">JN Cao</name>
</author>
<author><name sortKey="Su, H" uniqKey="Su H">H Su</name>
</author>
<author><name sortKey="Osann, K" uniqKey="Osann K">K Osann</name>
</author>
<author><name sortKey="Gupta, S" uniqKey="Gupta S">S Gupta</name>
</author>
</analytic>
</biblStruct>
<biblStruct><analytic><author><name sortKey="Franceschi, C" uniqKey="Franceschi C">C Franceschi</name>
</author>
<author><name sortKey="Monti, D" uniqKey="Monti D">D Monti</name>
</author>
<author><name sortKey="Sansoni, P" uniqKey="Sansoni P">P Sansoni</name>
</author>
<author><name sortKey="Cossarizza, A" uniqKey="Cossarizza A">A Cossarizza</name>
</author>
</analytic>
</biblStruct>
<biblStruct><analytic><author><name sortKey="Jacquelin, B" uniqKey="Jacquelin B">B Jacquelin</name>
</author>
<author><name sortKey="Mayau, V" uniqKey="Mayau V">V Mayau</name>
</author>
<author><name sortKey="Brysbaert, G" uniqKey="Brysbaert G">G Brysbaert</name>
</author>
<author><name sortKey="Regnault, B" uniqKey="Regnault B">B Regnault</name>
</author>
<author><name sortKey="Diop, Om" uniqKey="Diop O">OM Diop</name>
</author>
<author><name sortKey="Arenzana Seisdedos, F" uniqKey="Arenzana Seisdedos F">F Arenzana-Seisdedos</name>
</author>
<author><name sortKey="Rogge, L" uniqKey="Rogge L">L Rogge</name>
</author>
<author><name sortKey="Coppee, Jy" uniqKey="Coppee J">JY Coppee</name>
</author>
<author><name sortKey="Barre Sinoussi, F" uniqKey="Barre Sinoussi F">F Barre-Sinoussi</name>
</author>
<author><name sortKey="Benecke, A" uniqKey="Benecke A">A Benecke</name>
</author>
<author><name sortKey="Muller Trutwin, Mc" uniqKey="Muller Trutwin M">MC Muller-Trutwin</name>
</author>
</analytic>
</biblStruct>
<biblStruct><analytic><author><name sortKey="Clay, Cc" uniqKey="Clay C">CC Clay</name>
</author>
<author><name sortKey="Rodrigues, Ds" uniqKey="Rodrigues D">DS Rodrigues</name>
</author>
<author><name sortKey="Brignolo, Ll" uniqKey="Brignolo L">LL Brignolo</name>
</author>
<author><name sortKey="Spinner, A" uniqKey="Spinner A">A Spinner</name>
</author>
<author><name sortKey="Tarara, Rp" uniqKey="Tarara R">RP Tarara</name>
</author>
<author><name sortKey="Plopper, Cg" uniqKey="Plopper C">CG Plopper</name>
</author>
<author><name sortKey="Leutenegger, Cm" uniqKey="Leutenegger C">CM Leutenegger</name>
</author>
<author><name sortKey="Esser, U" uniqKey="Esser U">U Esser</name>
</author>
</analytic>
</biblStruct>
<biblStruct><analytic><author><name sortKey="Beaumier, Cm" uniqKey="Beaumier C">CM Beaumier</name>
</author>
<author><name sortKey="Harris, Ld" uniqKey="Harris L">LD Harris</name>
</author>
<author><name sortKey="Goldstein, S" uniqKey="Goldstein S">S Goldstein</name>
</author>
<author><name sortKey="Klatt, Nr" uniqKey="Klatt N">NR Klatt</name>
</author>
<author><name sortKey="Whitted, S" uniqKey="Whitted S">S Whitted</name>
</author>
<author><name sortKey="Mcginty, J" uniqKey="Mcginty J">J McGinty</name>
</author>
<author><name sortKey="Apetrei, C" uniqKey="Apetrei C">C Apetrei</name>
</author>
<author><name sortKey="Pandrea, I" uniqKey="Pandrea I">I Pandrea</name>
</author>
<author><name sortKey="Hirsch, Vm" uniqKey="Hirsch V">VM Hirsch</name>
</author>
<author><name sortKey="Brenchley, Jm" uniqKey="Brenchley J">JM Brenchley</name>
</author>
</analytic>
</biblStruct>
<biblStruct><analytic><author><name sortKey="Murayama, Y" uniqKey="Murayama Y">Y Murayama</name>
</author>
<author><name sortKey="Mukai, R" uniqKey="Mukai R">R Mukai</name>
</author>
<author><name sortKey="Inoue Murayama, M" uniqKey="Inoue Murayama M">M Inoue-Murayama</name>
</author>
<author><name sortKey="Yoshikawa, Y" uniqKey="Yoshikawa Y">Y Yoshikawa</name>
</author>
</analytic>
</biblStruct>
<biblStruct><analytic><author><name sortKey="Murayama, Y" uniqKey="Murayama Y">Y Murayama</name>
</author>
<author><name sortKey="Amano, A" uniqKey="Amano A">A Amano</name>
</author>
<author><name sortKey="Mukai, R" uniqKey="Mukai R">R Mukai</name>
</author>
<author><name sortKey="Shibata, H" uniqKey="Shibata H">H Shibata</name>
</author>
<author><name sortKey="Matsunaga, S" uniqKey="Matsunaga S">S Matsunaga</name>
</author>
<author><name sortKey="Takahashi, H" uniqKey="Takahashi H">H Takahashi</name>
</author>
<author><name sortKey="Yoshikawa, Y" uniqKey="Yoshikawa Y">Y Yoshikawa</name>
</author>
<author><name sortKey="Hayami, M" uniqKey="Hayami M">M Hayami</name>
</author>
<author><name sortKey="Noguchi, A" uniqKey="Noguchi A">A Noguchi</name>
</author>
</analytic>
</biblStruct>
<biblStruct><analytic><author><name sortKey="Mcauliffe, J" uniqKey="Mcauliffe J">J McAuliffe</name>
</author>
<author><name sortKey="Vogel, L" uniqKey="Vogel L">L Vogel</name>
</author>
<author><name sortKey="Roberts, A" uniqKey="Roberts A">A Roberts</name>
</author>
<author><name sortKey="Fahle, G" uniqKey="Fahle G">G Fahle</name>
</author>
<author><name sortKey="Fischer, S" uniqKey="Fischer S">S Fischer</name>
</author>
<author><name sortKey="Shieh, Wj" uniqKey="Shieh W">WJ Shieh</name>
</author>
<author><name sortKey="Butler, E" uniqKey="Butler E">E Butler</name>
</author>
<author><name sortKey="Zaki, S" uniqKey="Zaki S">S Zaki</name>
</author>
<author><name sortKey="St Claire, M" uniqKey="St Claire M">M St Claire</name>
</author>
<author><name sortKey="Murphy, B" uniqKey="Murphy B">B Murphy</name>
</author>
<author><name sortKey="Subbarao, K" uniqKey="Subbarao K">K Subbarao</name>
</author>
</analytic>
</biblStruct>
<biblStruct><analytic><author><name sortKey="Coates, Pt" uniqKey="Coates P">PT Coates</name>
</author>
<author><name sortKey="Barratt Boyes, Sm" uniqKey="Barratt Boyes S">SM Barratt-Boyes</name>
</author>
<author><name sortKey="Zhang, L" uniqKey="Zhang L">L Zhang</name>
</author>
<author><name sortKey="Donnenberg, Vs" uniqKey="Donnenberg V">VS Donnenberg</name>
</author>
<author><name sortKey="O Onnell, Pj" uniqKey="O Onnell P">PJ O’Connell</name>
</author>
<author><name sortKey="Logar, Aj" uniqKey="Logar A">AJ Logar</name>
</author>
<author><name sortKey="Duncan, Fj" uniqKey="Duncan F">FJ Duncan</name>
</author>
<author><name sortKey="Murphey Corb, M" uniqKey="Murphey Corb M">M Murphey-Corb</name>
</author>
<author><name sortKey="Donnenberg, Ad" uniqKey="Donnenberg A">AD Donnenberg</name>
</author>
<author><name sortKey="Morelli, Ae" uniqKey="Morelli A">AE Morelli</name>
</author>
<author><name sortKey="Maliszewski, Cr" uniqKey="Maliszewski C">CR Maliszewski</name>
</author>
<author><name sortKey="Thomson, Aw" uniqKey="Thomson A">AW Thomson</name>
</author>
</analytic>
</biblStruct>
<biblStruct><analytic><author><name sortKey="Wykrzykowska, Jj" uniqKey="Wykrzykowska J">JJ Wykrzykowska</name>
</author>
<author><name sortKey="Pauley, Dr" uniqKey="Pauley D">DR Pauley</name>
</author>
<author><name sortKey="Lackner, Aa" uniqKey="Lackner A">AA Lackner</name>
</author>
<author><name sortKey="Simon, Ma" uniqKey="Simon M">MA Simon</name>
</author>
</analytic>
</biblStruct>
<biblStruct><analytic><author><name sortKey="Sallusto, F" uniqKey="Sallusto F">F Sallusto</name>
</author>
<author><name sortKey="Lenig, D" uniqKey="Lenig D">D Lenig</name>
</author>
<author><name sortKey="Forster, R" uniqKey="Forster R">R Forster</name>
</author>
<author><name sortKey="Lipp, M" uniqKey="Lipp M">M Lipp</name>
</author>
<author><name sortKey="Lanzavecchia, A" uniqKey="Lanzavecchia A">A Lanzavecchia</name>
</author>
</analytic>
</biblStruct>
<biblStruct><analytic><author><name sortKey="Koch, S" uniqKey="Koch S">S Koch</name>
</author>
<author><name sortKey="Larbi, A" uniqKey="Larbi A">A Larbi</name>
</author>
<author><name sortKey="Derhovanessian, E" uniqKey="Derhovanessian E">E Derhovanessian</name>
</author>
<author><name sortKey="Ozcelik, D" uniqKey="Ozcelik D">D Ozcelik</name>
</author>
<author><name sortKey="Naumova, E" uniqKey="Naumova E">E Naumova</name>
</author>
<author><name sortKey="Pawelec, G" uniqKey="Pawelec G">G Pawelec</name>
</author>
</analytic>
</biblStruct>
<biblStruct><analytic><author><name sortKey="Kaufmann, A" uniqKey="Kaufmann A">A Kaufmann</name>
</author>
<author><name sortKey="Salentin, R" uniqKey="Salentin R">R Salentin</name>
</author>
<author><name sortKey="Gemsa, D" uniqKey="Gemsa D">D Gemsa</name>
</author>
<author><name sortKey="Sprenger, H" uniqKey="Sprenger H">H Sprenger</name>
</author>
</analytic>
</biblStruct>
<biblStruct><analytic><author><name sortKey="Katschke, Kj" uniqKey="Katschke K">KJ Katschke</name>
</author>
<author><name sortKey="Rottman, Jb" uniqKey="Rottman J">JB Rottman</name>
</author>
<author><name sortKey="Ruth, Jh" uniqKey="Ruth J">JH Ruth</name>
</author>
<author><name sortKey="Qin, S" uniqKey="Qin S">S Qin</name>
</author>
<author><name sortKey="Wu, L" uniqKey="Wu L">L Wu</name>
</author>
<author><name sortKey="Larosa, G" uniqKey="Larosa G">G LaRosa</name>
</author>
<author><name sortKey="Ponath, P" uniqKey="Ponath P">P Ponath</name>
</author>
<author><name sortKey="Park, Cc" uniqKey="Park C">CC Park</name>
</author>
<author><name sortKey="Pope, Rm" uniqKey="Pope R">RM Pope</name>
</author>
<author><name sortKey="Koch, Ae" uniqKey="Koch A">AE Koch</name>
</author>
</analytic>
</biblStruct>
<biblStruct><analytic><author><name sortKey="Ziegler Heitbrock, L" uniqKey="Ziegler Heitbrock L">L Ziegler-Heitbrock</name>
</author>
</analytic>
</biblStruct>
<biblStruct><analytic><author><name sortKey="Mortara, L" uniqKey="Mortara L">L Mortara</name>
</author>
<author><name sortKey="Ploquin, Mj" uniqKey="Ploquin M">MJ Ploquin</name>
</author>
<author><name sortKey="Faye, A" uniqKey="Faye A">A Faye</name>
</author>
<author><name sortKey="Scott Algara, D" uniqKey="Scott Algara D">D Scott-Algara</name>
</author>
<author><name sortKey="Vaslin, B" uniqKey="Vaslin B">B Vaslin</name>
</author>
<author><name sortKey="Butor, C" uniqKey="Butor C">C Butor</name>
</author>
<author><name sortKey="Hosmalin, A" uniqKey="Hosmalin A">A Hosmalin</name>
</author>
<author><name sortKey="Barre Sinoussi, F" uniqKey="Barre Sinoussi F">F Barre-Sinoussi</name>
</author>
<author><name sortKey="Diop, Om" uniqKey="Diop O">OM Diop</name>
</author>
<author><name sortKey="Muller Trutwin, Mc" uniqKey="Muller Trutwin M">MC Muller-Trutwin</name>
</author>
</analytic>
</biblStruct>
</listBibl>
</div1>
</back>
</TEI>
<pmc article-type="research-article" xml:lang="en"><pmc-dir>properties open_access</pmc-dir>
<front><journal-meta><journal-id journal-id-type="nlm-ta">Immun Ageing</journal-id>
<journal-id journal-id-type="iso-abbrev">Immun Ageing</journal-id>
<journal-title-group><journal-title>Immunity & Ageing : I & A</journal-title>
</journal-title-group>
<issn pub-type="epub">1742-4933</issn>
<publisher><publisher-name>BioMed Central</publisher-name>
</publisher>
</journal-meta>
<article-meta><article-id pub-id-type="pmid">24642138</article-id>
<article-id pub-id-type="pmc">3999990</article-id>
<article-id pub-id-type="publisher-id">1742-4933-11-4</article-id>
<article-id pub-id-type="doi">10.1186/1742-4933-11-4</article-id>
<article-categories><subj-group subj-group-type="heading"><subject>Research</subject>
</subj-group>
</article-categories>
<title-group><article-title>Severe acute respiratory syndrome-coronavirus infection in aged nonhuman primates is associated with modulated pulmonary and systemic immune responses</article-title>
</title-group>
<contrib-group><contrib contrib-type="author" id="A1"><name><surname>Clay</surname>
<given-names>Candice C</given-names>
</name>
<xref ref-type="aff" rid="I1">1</xref>
<xref ref-type="aff" rid="I2">2</xref>
<email>ccclay@primate.ucdavis.edu</email>
</contrib>
<contrib contrib-type="author" id="A2"><name><surname>Donart</surname>
<given-names>Nathan</given-names>
</name>
<xref ref-type="aff" rid="I1">1</xref>
<email>ndonart@lrri.org</email>
</contrib>
<contrib contrib-type="author" id="A3"><name><surname>Fomukong</surname>
<given-names>Ndingsa</given-names>
</name>
<xref ref-type="aff" rid="I1">1</xref>
<email>ndingsafomukong@yahoo.com</email>
</contrib>
<contrib contrib-type="author" id="A4"><name><surname>Knight</surname>
<given-names>Jennifer B</given-names>
</name>
<xref ref-type="aff" rid="I1">1</xref>
<email>jknight@lrri.org</email>
</contrib>
<contrib contrib-type="author" id="A5"><name><surname>Overheim</surname>
<given-names>Katie</given-names>
</name>
<xref ref-type="aff" rid="I1">1</xref>
<email>koverheim@atcc.org</email>
</contrib>
<contrib contrib-type="author" id="A6"><name><surname>Tipper</surname>
<given-names>Jennifer</given-names>
</name>
<xref ref-type="aff" rid="I1">1</xref>
<email>jtipper@lrri.org</email>
</contrib>
<contrib contrib-type="author" id="A7"><name><surname>Van Westrienen</surname>
<given-names>Jesse</given-names>
</name>
<xref ref-type="aff" rid="I1">1</xref>
<email>jessewvw@gmail.com</email>
</contrib>
<contrib contrib-type="author" id="A8"><name><surname>Hahn</surname>
<given-names>Fletcher</given-names>
</name>
<xref ref-type="aff" rid="I1">1</xref>
<email>FHahn@lrri.org</email>
</contrib>
<contrib contrib-type="author" corresp="yes" id="A9"><name><surname>Harrod</surname>
<given-names>Kevin S</given-names>
</name>
<xref ref-type="aff" rid="I1">1</xref>
<email>Kharrod@LRRI.org</email>
</contrib>
</contrib-group>
<aff id="I1"><label>1</label>
Work performed at Lovelace Respiratory Research Institute (LRRI), Infectious Disease Program, Albuquerque, NM, Mexico</aff>
<aff id="I2"><label>2</label>
California National Primate Research Center, University of California, Davis, CA, USA</aff>
<pub-date pub-type="collection"><year>2014</year>
</pub-date>
<pub-date pub-type="epub"><day>19</day>
<month>3</month>
<year>2014</year>
</pub-date>
<volume>11</volume>
<fpage>4</fpage>
<lpage>4</lpage>
<history><date date-type="received"><day>29</day>
<month>8</month>
<year>2013</year>
</date>
<date date-type="accepted"><day>6</day>
<month>3</month>
<year>2014</year>
</date>
</history>
<permissions><copyright-statement>Copyright © 2014 Clay et al.; licensee BioMed Central Ltd.</copyright-statement>
<copyright-year>2014</copyright-year>
<copyright-holder>Clay et al.; licensee BioMed Central Ltd.</copyright-holder>
<license license-type="open-access" xlink:href="http://creativecommons.org/licenses/by/2.0"><license-p>This is an Open Access article distributed under the terms of the Creative Commons Attribution License (<ext-link ext-link-type="uri" xlink:href="http://creativecommons.org/licenses/by/2.0">http://creativecommons.org/licenses/by/2.0</ext-link>
), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly credited.</license-p>
</license>
</permissions>
<self-uri xlink:href="http://www.immunityageing.com/content/11/1/4"></self-uri>
<abstract><sec><title>Background</title>
<p>Many respiratory viruses disproportionately impact the elderly. Likewise, advanced age correlated with more adverse disease outcomes following severe acute respiratory syndrome coronavirus (SARS-CoV) infection in humans. We used an aged African green monkey SARS-CoV infection model to better understand age-related mechanisms of increased susceptibility to viral respiratory infections. Nonhuman primates are critical translational models for such research given their similarities to humans in immune-ageing as well as lung structure.</p>
</sec>
<sec><title>Results</title>
<p>Significant age- and infection-dependent differences were observed in both systemic and mucosal immune compartments. Peripheral lymphocytes, specifically CD8 T and B cells were significantly lower in aged monkeys pre- and post- SARS-CoV infection, while neutrophil and monocyte numbers were not impacted by age or infection status. Serum proinflammatory cytokines were similar in both age groups, whereas significantly lower levels of IL-1beta, IL-18, IL-6, IL-12 and IL-15 were detected in the lungs of SARS-CoV-infected aged monkeys at either 5 or 10 days post infection. Total lung leukocyte numbers and relative frequency of CD8 T cells, B cells, macrophages and dendritic cells were greatly reduced in the aged host during SARS-CoV infection, despite high levels of chemoattractants for many of these cells in the aged lung. Dendritic cells and monocytes/macrophages showed age-dependent differences in activation and chemokine receptor profiles, while the CD8 T cell and B cell responses were significantly reduced in the aged host. In examination of viral titers, significantly higher levels of SARS-CoV were detected in the nasal swabs early, at day 1 post infection, in aged as compared to juvenile monkeys, but virus levels were only slightly higher in aged animals by day 3. Although there was a trend of higher titers in respiratory tissues at day 5 post infection, this did not reach statistical significance and virus was cleared from all animals by day 10, regardless of age.</p>
</sec>
<sec><title>Conclusions</title>
<p>This study provides unique insight into how several parameters of the systemic and mucosal immune response to SARS-CoV infection are significantly modulated by age. These immune differences may contribute to deficient immune function and the observed trend of higher SARS-CoV replication in aged nonhuman primates.</p>
</sec>
</abstract>
</article-meta>
</front>
</pmc>
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