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Human Immunodeficiency Virus Type 2: The Neglected Threat.

ABSTRACT: West Africa has the highest prevalence of human immunodeficiency virus (HIV)-2 infection in the world, but a high number of cases has been recognized in Europe, India, and the United States. The virus is less transmissible than HIV-1, with sexual contacts being the most frequent route of acquisition. In the absence of specific antiretroviral therapy, most HIV-2 carriers will develop AIDS. Although, it requires more time than HIV-1 infection, CD4+ T cell decline occurs more slowly in HIV-2 than in HIV-1 patients. HIV-2 is resistant to non-nucleoside reverse transcriptase inhibitors (NNRTIs) and some protease inhibitors. Misdiagnosis of HIV-2 in patients mistakenly considered HIV-1-positive or in those with dual infections can cause treatment failures with undetectable HIV-1 RNA. In this era of global integration, clinicians must be aware of when to consider the diagnosis of HIV-2 infection and how to test for this virus. Although there is debate regarding when therapy should be initiated and which regimen should be chosen, recent trials have provided important information on treatment options for HIV-2 infection. In this review, we focus mainly on data available and on the insight they offer about molecular epidemiology, clinical presentation, antiretroviral therapy, and diagnostic tests of HIV-2 infection.

SUBMITTER: Ceccarelli G

PROVIDER: S-EPMC8621479 | biostudies-literature |

REPOSITORIES: biostudies-literature

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Project description:The host restriction factor tetherin inhibits virion release from infected cells and poses a significant barrier to successful zoonotic transmission of primate lentiviruses to humans. While most simian immunodeficiency viruses (SIV), including the direct precursors of human immunodeficiency virus type 1 (HIV-1) and HIV-2, use their Nef protein to counteract tetherin in their natural hosts, they fail to antagonize the human tetherin ortholog. Pandemic HIV-1 group M and epidemic group O strains overcame this hurdle by adapting their Vpu and Nef proteins, respectively, whereas HIV-2 group A uses its envelope (Env) glycoprotein to counteract human tetherin. Whether or how the remaining eight groups of HIV-2 antagonize this antiviral factor has remained unclear. Here, we show that Nef proteins from diverse groups of HIV-2 do not or only modestly antagonize human tetherin, while their ability to downmodulate CD3 and CD4 is highly conserved. Experiments in transfected cell lines and infected primary cells revealed that not only Env proteins of epidemic HIV-2 group A but also those of a circulating recombinant form (CRF01_AB) and rare groups F and I decrease surface expression of human tetherin and significantly enhance progeny virus release. Intriguingly, we found that many SIVsmm Envs also counteract human as well as smm tetherin. Thus, Env-mediated tetherin antagonism in different groups of HIV-2 presumably stems from a preadaptation of their SIVsmm precursors to humans. In summary, we identified a phenotypic trait of SIVsmm that may have facilitated its successful zoonotic transmission to humans and the emergence of HIV-2.IMPORTANCE 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.

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Human Immunodeficiency Virus Type 2: The Neglected Threat.

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