Preadaptation of Simian Immunodeficiency Virus SIVsmm Facilitated Env-Mediated Counteraction of Human Tetherin by Human Immunodeficiency Virus Type 2

Abstract

HIV-2 groups A to I resulted from nine independent cross-species transmission events of SIVsmm to humans and differ considerably in their prevalence and geographic spread. Thus, detailed characterization of these viruses offers a valuable means to elucidate immune evasion mechanisms and human-specific adaptations determining viral spread. In a systematic comparison of rare and epidemic HIV-2 groups and their simian SIVsmm counterparts, we found that the ability of Nef to downmodulate the primary viral entry receptor CD4 and the T cell receptor CD3 is conserved, while effects on CD28, CD74, and major histocompatibility complex class I surface expression vary considerably. Furthermore, we show that not only the Env proteins of HIV-2 groups A, AB, F, and I but also those of some SIVsmm isolates antagonize human tetherin. This finding helps to explain why SIVsmm has been able to cross the species barrier to humans on at least nine independent occasions.