Vif Proteins from Diverse Primate Lentiviral Lineages Use the Same Binding Site in APOBEC3G

Letko, Michael; Silvestri, Guido; Hahn, Beatrice H.; Bibollet-Ruche, F.; Gökçümen, Ömer; Simon, Viviana; Ooms, Marcel

doi:10.1128/jvi.01944-13

Cited by 38 publications

(71 citation statements)

References 64 publications

(113 reference statements)

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Although all gorillas we have examined are homozygous at the site in A3G conferring resistance to SIVcpz, extensive A3G sequence diversity has been observed in other primate species (e.g., rhesus macaques, sooty mangabeys, African green monkeys) (40,41). A3G polymorphism could render certain individuals more susceptible to transmissions of SIVcpz, allowing the virus to gain a foothold in gorillas (19). It is also possible that the spread of SIVgor selected Fig.…”

Section: Sivgor Resulted From a Single Introduction Of Sivcpz From Symentioning

confidence: 99%

“…One potential restriction factor is APOBEC3G (A3G), which is normally counteracted by the Vif protein of HIV-1 and SIVcpz, leading to its degradation. However, we had previously observed that a Pro (P)-to-Gln (Q) change at site 129 in the gorilla A3G protein confers resistance to Vif-mediated degradation by some HIV-1 and SIVcpz strains (19). To examine this result further, we tested the anti-A3G activity of a larger panel of Vif proteins from both SIVcpzPtt (from P. t. troglodytes) and SIVcpzPts (from P. t. scheinfurthii) strains.…”

Section: Full-length Genome Sequencing Of Sivgor Strains Closely Relamentioning

confidence: 99%

“…C-terminally FLAG-tagged expression plasmids of SIVcpzPts (TAN1 and TAN2), SIVcpzPtt (EK505 and LB715), and SIVgor (CP2139) vif genes; a ΔVif-GFP control construct; and HAtagged chimpanzee and gorilla A3G expression plasmids have been described (19). Vif alleles from SIVcpzPtt MT145 (4), SIVcpzPtt GAB2 (61,62), SIVcpzPts TAN3 (63), and SIVcpzPts TAN13 (63) were amplified from fulllength molecular clones and cloned into the pCRV1 Vif-expression plasmid (19). Increasing amounts of HA-tagged A3G (0, 25, 50, and 100 ng) and Vif-expression (or ΔVif-GFP for control) plasmids (50 ng) were cotransfected with NL4-3 ΔVif (500 ng) in 293T cells.…”

Section: Resistance Testing Of Gorilla A3g To Degradation By Sivcpz Amentioning

confidence: 99%

See 2 more Smart Citations

Origin of the HIV-1 group O epidemic in western lowland gorillas

D’arc

Ayouba

Esteban

et al. 2015

Proc. Natl. Acad. Sci. U.S.A.

Self Cite

134

149

View full text Add to dashboard Cite

HIV-1, the cause of AIDS, is composed of four phylogenetic lineages, groups M, N, O, and P, each of which resulted from an independent cross-species transmission event of simian immunodeficiency viruses (SIVs) infecting African apes. Although groups M and N have been traced to geographically distinct chimpanzee communities in southern Cameroon, the reservoirs of groups O and P remain unknown. Here, we screened fecal samples from western lowland (n = 2,611), eastern lowland (n = 103), and mountain (n = 218) gorillas for gorilla SIV (SIVgor) antibodies and nucleic acids. Despite testing wild troops throughout southern Cameroon (n = 14), northern Gabon (n = 16), the Democratic Republic of Congo (n = 2), and Uganda (n = 1), SIVgor was identified at only four sites in southern Cameroon, with prevalences ranging from 0.8–22%. Amplification of partial and full-length SIVgor sequences revealed extensive genetic diversity, but all SIVgor strains were derived from a single lineage within the chimpanzee SIV (SIVcpz) radiation. Two fully sequenced gorilla viruses from southwestern Cameroon were very closely related to, and likely represent the source population of, HIV-1 group P. Most of the genome of a third SIVgor strain, from central Cameroon, was very closely related to HIV-1 group O, again pointing to gorillas as the immediate source. Functional analyses identified the cytidine deaminase APOBEC3G as a barrier for chimpanzee-to-gorilla, but not gorilla-to-human, virus transmission. These data indicate that HIV-1 group O, which spreads epidemically in west central Africa and is estimated to have infected around 100,000 people, originated by cross-species transmission from western lowland gorillas.

show abstract

Section: Sivgor Resulted From a Single Introduction Of Sivcpz From Symentioning

confidence: 99%

Section: Full-length Genome Sequencing Of Sivgor Strains Closely Relamentioning

confidence: 99%

Section: Resistance Testing Of Gorilla A3g To Degradation By Sivcpz Amentioning

confidence: 99%

See 1 more Smart Citation

Origin of the HIV-1 group O epidemic in western lowland gorillas

D’arc

Ayouba

Esteban

et al. 2015

Proc. Natl. Acad. Sci. U.S.A.

Self Cite

134

149

View full text Add to dashboard Cite

show abstract

“…Unlike APOBEC3-Vif1 interactions, very few studies have attempted to define the interactions between HIV-2 Vif (Vif2) and the APOBEC3 proteins (11,13). There is only ϳ30% amino acid identity between Vif1 from NL4-3 and Vif2 from HIV-2 ROD12 .…”

mentioning

confidence: 99%

“…Members of the human apolipoprotein B mRNAediting enzyme catalytic polypeptide-like 3 (APOBEC3 [A3]) family of proteins are potent cellular restriction factors that provide a defense against viral infection by incorporating into virions and targeting nascent viral DNA for deamination of cytidine residues to uridines (1)(2)(3)(4)(5)(6)(7)(8); cytidine deamination of the viral DNA leads to lethal hypermutation of the targeted virus. However, both HIV-1 and HIV-2 have accessory proteins, called viral infectivity factors (Vifs), that can bind to the APOBEC3 proteins to promote their ubiquitination and subsequent proteosomal degradation (9)(10)(11)(12)(13)(14)(15)(16)(17)(18), thereby suppressing their virion incorporation.…”

mentioning

confidence: 99%

HIV-1 and HIV-2 Vif Interact with Human APOBEC3 Proteins Using Completely Different Determinants

Smith

Izumi

Borbet

et al. 2014

J Virol

View full text Add to dashboard Cite

Human APOBEC3 (A3) restriction factors provide intrinsic immunity against zoonotic transmission of pathogenic viruses. A3D, A3F, A3G, and A3H haplotype II (A3H-hapII) can be packaged into virion infectivity factor (Vif)-deficient HIVs to inhibit viral replication. To overcome these restriction factors, Vif binds to the A3 proteins in viral producer cells to target them for ubiquitination and proteasomal degradation, thus preventing their packaging into assembling virions. Therefore, the Vif-A3 interactions are attractive targets for novel drug development. HIV-1 and HIV-2 arose via distinct zoonotic transmission events of simian immunodeficiency viruses from chimpanzees and sooty mangabeys, respectively, and Vifs from these viruses have limited homology. To gain insights into the evolution of virus-host interactions that led to successful cross-species transmission of lentiviruses, we characterized the determinants of the interaction between HIV-2 Vif (Vif2) with human A3 proteins and compared them to the previously identified HIV-1 Vif (Vif1) interactions with the A3 proteins. We found that A3G, A3F, and A3H-hapII, but not A3D, were susceptible to Vif2-induced degradation. Alanine-scanning mutational analysis of the first 62 amino acids of Vif2 indicated that Vif2 determinants important for degradation of A3G and A3F are completely distinct from these regions in Vif1, as are the determinants in A3G and A3F that are critical for Vif2-induced degradation. These observations suggest that distinct Vif-A3 interactions evolved independently in different SIVs and their nonhuman primate hosts and conservation of the A3 determinants targeted by the SIV Vif proteins resulted in successful zoonotic transmission into humans. IMPORTANCEPrimate APOBEC3 proteins provide innate immunity against invading pathogens, and Vif proteins of primate lentiviruses have evolved to overcome these host defenses by interacting with them and inducing their proteasomal degradation. HIV-1 and HIV-2 are two human pathogens that induce AIDS, and elucidating interactions between their Vif proteins and human A3 proteins could facilitate the development of novel antiviral drugs. Furthermore, understanding Vif-A3 interactions can provide novel insights into the cross-species transmission events that led to the HIV-1 and HIV-2 pandemics and evolution of host-virus interactions. We carried out mutational analysis of the N-terminal 62 amino acids of HIV-2 Vif (Vif2) and analyzed A3G/A3F chimeras that retained antiviral activity to identify the determinants of the Vif2 and A3 interaction. Our results show that the Vif2-A3 interactions are completely different from the Vif1-A3 interactions, suggesting that these interactions evolved independently and that conservation of the A3 determinants resulted in successful zoonotic transmission into humans.

show abstract

Polymorphisms in the APOBEC3G gene of Chinese rhesus macaques affect resistance to ubiquitination and degradation mediated by HIV-2 Vif

Jiang

Yao

et al. 2019

Arch Virol

View full text Add to dashboard Cite

Animal cells have multiple innate effector mechanisms that inhibit viral replication. For the pathogenic retrovirus human immunodeficiency virus 1 (HIV-1), there are widely expressed restriction factors, such as APOBEC3 proteins, tetherin/ BST2, SAMHD1 and MX2, as well as TRIM5α. We previously found that the TRIM5α gene clearly affects SIVmac or HIV-2 replication, but the major determinant of the combinatorial effect caused by multiple host restriction factors is still not fully clear. APOBEC3G (apolipoprotein B mRNA editing enzyme, catalytic polypeptide-like 3G), a host restriction factor that restricts HIV replication by causing cytosine deamination, can be targeted and degraded by the SIV/HIV-1/HIV-2 accessory protein Vif. Although rhesus macaques are widely used in HIV/AIDS research, little is known regarding the impact of APOBEC3G gene polymorphisms on viral Vif-mediated ubiquitin degradation in Chinese-origin rhesus macaques. In this study, we therefore genotyped APOBEC3G in 35 Chinese rhesus macaques. We identified a novel transcript and 27 APOBEC3G polymorphisms, including 20 non-synonymous variants and 7 synonymous mutation sites, of which 10 were novel. According to the predicted structure of the A3G protein, we predicted that the E88K and G212D mutations, both on the surface of the A3G protein, would have a significant effect on Vif-induced A3G degradation. However, an in vitro overexpression assay showed that these mutations did not influence HIV-2-Vif-mediated degradation of APOBEC3G. Unexpectedly, another polymorphism L71R, conferred resistance to Vif-mediated ubiquitin degradation, strongly suggesting that L71R might play an important role in antiviral defense mechanisms.

show abstract

Vif Proteins from Diverse Primate Lentiviral Lineages Use the Same Binding Site in APOBEC3G

Cited by 38 publications

References 64 publications

Origin of the HIV-1 group O epidemic in western lowland gorillas

Origin of the HIV-1 group O epidemic in western lowland gorillas

HIV-1 and HIV-2 Vif Interact with Human APOBEC3 Proteins Using Completely Different Determinants

Polymorphisms in the APOBEC3G gene of Chinese rhesus macaques affect resistance to ubiquitination and degradation mediated by HIV-2 Vif

Contact Info

Product

Resources

About