A novel proviral clone of HIV-2: Biological and phylogenetic relationship to other primate immunodeficiency viruses

Kirchhoff, Frank; Jentsch, Klaus Dieter; Bachmann, Barbara J.; Stuke, Andreas W.; Laloux, Carine; Lüke, Wolfgang; Stahl–Hennig∥, Christiane; Schneider, Josef; Nieselt, Katja; Eigen, Manfred; Hunsmann, Gerhard

doi:10.1016/0042-6822(90)90484-9

Cited by 45 publications

(29 citation statements)

References 35 publications

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“…The SIVsm nef alleles were amplified directly from uncultured blood samples of naturally infected sooty mangabeys. Three of the HIV-2 nef alleles were derived from the infectious molecular ROD10 (9, 41), BEN (30), and CBL23 (53) clones. The remaining nef genes were amplified from the HIV-2 CDC 310248, 310072, 310319, and 60415K strains (16,42) obtained through the AIDS Reagent Program.…”

Section: Resultsmentioning

confidence: 99%

Primary Sooty Mangabey Simian Immunodeficiency Virus and Human Immunodeficiency Virus Type 2nefAlleles Modulate Cell Surface Expression of Various Human Receptors and Enhance Viral Infectivity and Replication

Münch

Schindler

Wildum

et al. 2005

J Virol

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The nef gene of the pathogenic simian immunodeficiency virus (SIV) mac239 clone has been well characterized. Little is known, however, about the function of nef alleles derived from naturally SIVsm-infected sooty mangabeys (Cercocebus atys) and from human immunodeficiency virus type 2 (HIV-2)-infected individuals.Addressing this, we demonstrate that, similarly to the SIVmac239 nef, primary SIVsm and HIV-2 nef alleles down-modulate cell surface expression of human CD4, CD28, CD3, and class I or II major histocompatibility complex (MHC-I or MHC-II, respectively) molecules, up-regulate surface expression of the invariant chain (Ii) associated with immature MHC-II, inhibit early T-cell activation events, and enhance virion infectivity. Both also stimulate viral replication, although HIV-2 nef alleles were less active in this assay than SIVsm nef alleles. Mutational analysis showed that a dileucine-based sorting motif in the C-proximal loop of SIV or HIV-2 Nef is critical for its effects on CD4, CD28, and Ii but dispensable for down-regulation of CD3, MHC-I, and MHC-II. The C terminus of SIV and HIV-2 Nef was exclusively required for down-modulation of MHC-I, further demonstrating that analogous functions are mediated by different domains in Nef proteins derived from different groups of primate lentiviruses.Our results demonstrate that none of the eight Nef functions investigated had been newly acquired after cross-species transmission of SIVsm from naturally infected mangabeys to humans or macaques. Notably, HIV-2 and SIVsm nef alleles efficiently down-modulate CD3 and C28 surface expression and inhibit T-cell activation more efficiently than HIV-1 nef alleles. These differences in Nef function might contribute to the relatively low levels of immune activation observed in HIV-2-infected human individuals.

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Section: Resultsmentioning

confidence: 99%

Primary Sooty Mangabey Simian Immunodeficiency Virus and Human Immunodeficiency Virus Type 2nefAlleles Modulate Cell Surface Expression of Various Human Receptors and Enhance Viral Infectivity and Replication

Münch

Schindler

Wildum

et al. 2005

J Virol

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“…The HIV-2 isolates that bound jacalin, Ben and UC1, have gp120 sequences that phylogenetically appear to represent a more recent introduction into the human population than the gp120 sequence of the NIH-Z isolate, to which jacalin did not bind (2,29,50). It appears that the O-linked carbohydrate attachment site in the middle of V1 for HIV-2 Ben and HIV-2 UC1 has been replaced with an N-linked attachment site for HIV-2 NIH-Z (Table 1).…”

Section: Discussionmentioning

confidence: 99%

Simian Immunodeficiency Virus from the Sooty Mangabey and Rhesus Macaque Is Modified with O-Linked Carbohydrate

Stansell

Canis

Haslam

et al. 2011

J Virol

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“…While HIV-2 NWK08 nef was directly amplified from patient DNA (5), SIVsmm FBr12w7, M926, M949, and G932 nef genes had been amplified by reverse transcription-PCR (RT-PCR) from the plasma of naturally infected sooty mangabeys, and FTq nef was isolated from the supernatant of an SIVsmm-infected sooty mangabey PBMC culture in previous studies (107,108). HIV-2 ROD10, BEN, 7312A, SIVsmm PGm5.3, and SIVmac 239 nef genes, as well as HIV-1 NL4-3 nef and vpu, were amplified from previously described proviral constructs (41,47,50,55,109). All remaining nef genes (SIVsmm D215, HIV-2 UC1, ALT, Abt96, 12034, and 07IC-TNP3) were synthesized by GenScript (Piscataway), Biomatik (Cambridge, Canada), or BaseClear (Leiden) according to published sequences.…”

Section: Methodsmentioning

confidence: 99%

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

Heusinger

Deppe

Sette

et al. 2018

J Virol

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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. 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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A novel proviral clone of HIV-2: Biological and phylogenetic relationship to other primate immunodeficiency viruses

Cited by 45 publications

References 35 publications

Primary Sooty Mangabey Simian Immunodeficiency Virus and Human Immunodeficiency Virus Type 2nefAlleles Modulate Cell Surface Expression of Various Human Receptors and Enhance Viral Infectivity and Replication

Primary Sooty Mangabey Simian Immunodeficiency Virus and Human Immunodeficiency Virus Type 2nefAlleles Modulate Cell Surface Expression of Various Human Receptors and Enhance Viral Infectivity and Replication

Simian Immunodeficiency Virus from the Sooty Mangabey and Rhesus Macaque Is Modified with O-Linked Carbohydrate

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

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