title: Evidence for a different susceptibility of primate lentiviruses to type I interferons.
abstract: Type I interferons induce a complex transcriptional program that leads to a generalized antiviral response against a large panel of viruses, including human immunodeficiency virus type 1 (HIV-1). However, despite the fact that interferons negatively regulate HIV-1 ex vivo, a chronic interferon state is linked to the progression of AIDS and to robust viral replication, rather than protection, in vivo. To explain this apparent contradiction, we hypothesized that HIV-1 may have evolved a partial resistance to interferon, and to test this hypothesis, we analyzed the effects of alpha interferon (IFN-α) on the infectivity of HIV-1, human immunodeficiency virus type 2 (HIV-2), and rhesus monkey simian immunodeficiency virus (SIVmac). The results we obtained indicate that HIV-1 is more resistant to an IFN-α-induced response than are HIV-2 and SIVmac. Our data indicate that the accumulation of viral DNA is more compromised following the infection of IFN-α-treated cells with HIV-2 and SIVmac than with HIV-1. This defect correlates with a faster destabilization of HIV-2 viral nucleoprotein complexes (VNCs), suggesting a link between VNC destabilization and impaired viral DNA (vDNA) accumulation. The differential susceptibilities to IFN-α of the primate lentiviruses tested here do not map to the capsid protein (CA), excluding de facto a role for human tripartite motif protein isoform 5 alpha (Trim5α) in this restriction; this also suggests that an additional restriction mechanism differentially affects primate lentivirus infection. The different behaviors of HIV-1 and HIV-2 with respect to IFN-α responses may account at least in part for the differences in pathogenesis observed between these two virus types.
authors.affiliation: Department of Human Virology, ENS-L, Lyon, France.
authors.forename: Stéphanie
authors.initials: S
authors.lastname: Cordeil
authors.forename: Xuan-Nhi
authors.initials: XN
authors.lastname: Nguyen
authors.forename: Gregory
authors.initials: G
authors.lastname: Berger
authors.forename: Stéphanie
authors.initials: S
authors.lastname: Durand
authors.forename: Michelle
authors.initials: M
authors.lastname: Ainouze
authors.forename: Andrea
authors.initials: A
authors.lastname: Cimarelli
mesh_terms: D036022:Capsid Proteins / Q000187:drug effects; D045744:Cell Line, Tumor; D004279:DNA, Viral / Q000235:genetics / Q000378:metabolism; D057809:HEK293 Cells; D015658:HIV Infections / Q000188:drug therapy / Q000821:virology; D015497:HIV-1 / Q000276:immunology / Q000502:physiology*; D015498:HIV-2 / Q000276:immunology / Q000502:physiology*; D006367:HeLa Cells; D054298:Human Immunodeficiency Virus Proteins / Q000378:metabolism; D006801:Humans; D016898:Interferon-alpha / Q000276:immunology*; D008264:Macrophages / Q000821:virology; D008562:Membrane Glycoproteins; D012191:Retroviridae Proteins / Q000378:metabolism; D015302:Simian Immunodeficiency Virus / Q000276:immunology / Q000502:physiology*; D014759:Viral Envelope Proteins; D017361:Viral Nonstructural Proteins / Q000378:metabolism; D014779:Virus Replication / Q000187:drug effects
chemical_list: D036022:Capsid Proteins; D004279:DNA, Viral; C028391:G protein, vesicular stomatitis virus; D054298:Human Immunodeficiency Virus Proteins; D016898:Interferon-alpha; D008562:Membrane Glycoproteins; D012191:Retroviridae Proteins; D014759:Viral Envelope Proteins; D017361:Viral Nonstructural Proteins