tetano
Editor, Senior Moderator
J Virol. 2012 Aug 1. [Epub ahead of print]
Increased viral loads and exacerbated innate host response in aged macaques infected with 2009 pandemic H1N1 influenza A virus.
Josset L, Engelmann F, Haberthur K, Kelly S, Park B, Kawoaka Y, Garc?a-Sastre A, Katze MG, Messaoudi I.
Source
Department of Microbiology, University of Washington, Seattle, WA, USA.
Abstract
In contrast to seasonal influenza infections, which typically cause significant morbidity and mortality in the elderly, the 2009 H1N1 virus caused severe infection in young adults. This phenomenon was attributed to the presence of cross-protective antibodies acquired by older individuals during previous exposures to H1N1 viruses. However, this hypothesis could not be empirically tested. To address this question, we compared viral replication and the development of the immune response in na?ve young and aged female rhesus macaques infected with A/California/04/2009 H1N1 (CA04). We show higher viral loads in the BAL, nasal and ocular swabs in aged animals, suggesting increased viral replication in both the lower and upper respiratory tracts. T cell proliferation was higher in the BAL, but delayed and reduced in peripheral blood in aged animals. This delay in proliferation correlated with a reduced frequency of effector CD4 T cells in old animals. Aged animals also mobilized inflammatory cytokines to higher levels in the BAL. Finally, we compared changes in gene expression using microarray analysis of BAL samples. Our analyses revealed that the largest difference in host response between aged and young animals was detected day 4 pi, with significantly higher induction of genes associated with inflammation and the innate immune response in aged animals. Overall, our data suggest that, in the absence of pre-existing antibodies, CA04 infection in aged macaques is associated with changes in innate and adaptive immune responses that were shown to correlate with increased disease severity in other respiratory disease models.
PMID:
22855494
[PubMed - as supplied by publisher]
http://www.ncbi.nlm.nih.gov/pubmed/22855494
Increased viral loads and exacerbated innate host response in aged macaques infected with 2009 pandemic H1N1 influenza A virus.
Josset L, Engelmann F, Haberthur K, Kelly S, Park B, Kawoaka Y, Garc?a-Sastre A, Katze MG, Messaoudi I.
Source
Department of Microbiology, University of Washington, Seattle, WA, USA.
Abstract
In contrast to seasonal influenza infections, which typically cause significant morbidity and mortality in the elderly, the 2009 H1N1 virus caused severe infection in young adults. This phenomenon was attributed to the presence of cross-protective antibodies acquired by older individuals during previous exposures to H1N1 viruses. However, this hypothesis could not be empirically tested. To address this question, we compared viral replication and the development of the immune response in na?ve young and aged female rhesus macaques infected with A/California/04/2009 H1N1 (CA04). We show higher viral loads in the BAL, nasal and ocular swabs in aged animals, suggesting increased viral replication in both the lower and upper respiratory tracts. T cell proliferation was higher in the BAL, but delayed and reduced in peripheral blood in aged animals. This delay in proliferation correlated with a reduced frequency of effector CD4 T cells in old animals. Aged animals also mobilized inflammatory cytokines to higher levels in the BAL. Finally, we compared changes in gene expression using microarray analysis of BAL samples. Our analyses revealed that the largest difference in host response between aged and young animals was detected day 4 pi, with significantly higher induction of genes associated with inflammation and the innate immune response in aged animals. Overall, our data suggest that, in the absence of pre-existing antibodies, CA04 infection in aged macaques is associated with changes in innate and adaptive immune responses that were shown to correlate with increased disease severity in other respiratory disease models.
PMID:
22855494
[PubMed - as supplied by publisher]
http://www.ncbi.nlm.nih.gov/pubmed/22855494