Nonpathogenic SIV infection of African green monkeys induces a strong but rapidly controlled type I IFN response.
African green monkeys (AGMs) infected with the AGM type of SIV (SIVagm) do not develop chronic immune activation and AIDS, despite viral loads similar to those detected in humans infected with HIV-1 and rhesus macaques (RMs) infected with the RM type of SIV (SIVmac). Because chronic immune activation drives progressive CD4+ T cell depletion and immune cell dysfunctions, factors that characterize disease progression, we sought to understand the molecular basis of this AGM phenotype. To this end, we longitudinally assessed the gene expression profiles of blood- and lymph node-derived CD4+ cells from AGMs and RMs in response to SIVagm and SIVmac infection, respectively, using a genomic microarray platform. The molecular signature of acute infection was characterized, in both species, by strong upregulation of type I IFN-stimulated genes (ISGs). ISG expression returned to basal levels after postinfection day 28 in AGMs but was sustained in RMs, especially in the lymph node-derived cells. We also found that SIVagm induced IFN-alpha production by AGM cells in vitro and that low IFN-alpha levels were sufficient to induce strong ISG responses. In conclusion, SIV infection triggered a rapid and strong IFN-alpha response in vivo in both AGMs and RMs, with this response being efficiently controlled only in AGMs, possibly as a result of active regulatory mechanisms.
Jacquelin
Béatrice
B
Institut Pasteur, Unité de Régulation des Infections Rétrovirales, Paris, France.
Mayau
Véronique
V
Targat
Brice
B
Liovat
Anne-Sophie
AS
Kunkel
Désirée
D
Petitjean
Gaël
G
Dillies
Marie-Agnès
MA
Roques
Pierre
P
Butor
Cécile
C
Silvestri
Guido
G
Giavedoni
Luis D
LD
Lebon
Pierre
P
Barré-Sinoussi
Françoise
F
Benecke
Arndt
A
Müller-Trutwin
Michaela C
MC
D000818:Animals; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology; D002522:Chlorocebus aethiops; D020869:Gene Expression Profiling; D015658:HIV Infections / Q000276:immunology / Q000821:virology; D015497:HIV-1; D054884:Host-Pathogen Interactions / Q000235:genetics / Q000276:immunology; D006801:Humans; D007370:Interferon Type I / Q000096:biosynthesis* / Q000235:genetics; D016898:Interferon-alpha / Q000096:biosynthesis / Q000235:genetics; D008253:Macaca mulatta; D020411:Oligonucleotide Array Sequence Analysis; D016097:Simian Acquired Immunodeficiency Syndrome / Q000235:genetics / Q000276:immunology* / Q000821:virology; D015302:Simian Immunodeficiency Virus / Q000235:genetics / Q000276:immunology* / Q000472:pathogenicity* / Q000502:physiology; D013045:Species Specificity; D014774:Virulence / Q000276:immunology; D014779:Virus Replication
D007370:Interferon Type I; D016898:Interferon-alpha