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Nef-mediated downmodulation of CD3 dampens immune activation and is critical for maintenance of high virus loads in SIV-infected macaques

ABSTRACT: The inability of Nef to downmodulate the T cell receptor CD3 distinguishes HIV-1 from most other primate lentiviruses and may contribute to its high virulence. However, the role of this Nef function in viral immune evasion and pathogenicity remained speculative. Here, we selectively disrupted this Nef activity in SIVmac239 and analyzed the consequences for the virological, immunological and clinical outcome of infection in rhesus macaques. The inability to downmodulate CD3 did not affect viral replication during acute infection but was associated with increased immune activation and antiviral gene expression. Thus, Nef-mediated downmodulation of CD3 dampens the inflammatory response to SIV infection and is critical for viral immune evasion.

ORGANISM(S): Macaca mulatta

PROVIDER: GSE141626 | GEO | 2020/03/09

REPOSITORIES: GEO

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