Ancestral reconstruction supports that loss of Nef-mediated T cell modulation coincided with the emergence of pathogenic lentiviruses.

ABSTRACT: Human immunodeficiency virus type 1 (HIV-1) originated following cross-species transmission of simian immunodeficiency virus (SIV) infecting chimpanzees (SIVcpz). While SIV infection of its natural primate hosts is typically non-pathogenic, SIVcpz/HIV-1 is highly pathogenic. SIV/HIV pathogenesis is influenced by the viral accessory protein Nef, which manipulates several immune factors to facilitate disease progression. Specifically, Nef can modulate T cell activation by downregulating the T cell receptor subunit CD3ζ and the co-stimulatory receptor CD28. Several studies have demonstrated that while Nef downregulates CD28 from the T cell surface, this ability is not completely conserved throughout the SIV/HIV phylogeny. In comparison, Nef-mediated CD3 downregulation is highly conserved in S

SUBMITTER: Baldino AM 

PROVIDER: S-EPMC12724223 | biostudies-literature | 2025 Dec

REPOSITORIES: biostudies-literature