Nef-Mediated CD3-TCR Downmodulation Dampens Acute Inflammation and Promotes SIV Immune Evasion (Cell Reports)

HIV-1 lacks the CD3 downmodulation function of Nef that is otherwise conserved in primate lentiviruses. Joas et al. disrupted this Nef activity in SIVmac239 and show that Nef-mediated downmodulation of CD3 dampens inflammatory responses to SIV. This promotes effective immune evasion and maintenance of high viral loads in infected rhesus macaques.