HIV-1 Vif inhibits G to A hypermutations catalyzed by virus-encapsidated APOBEC3G to maintain HIV-1 infectivity

Wang, Yudi; Kinlock, Ballington L.; Shao, Qiujia; Turner, Tiffany M; Liu, Bindong

doi:10.1186/s12977-014-0089-5

Cited by 14 publications

(9 citation statements)

References 47 publications

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“…As shown in Fig. 6C , HIV-1 Vif markedly degraded huA3G, as reported previously ( 45 , 50 , 51 ), and degraded tsA3Z1a, tsA3Z2a-Z2b, and tsA3Z2d-Z2e to a certain extent but did not degrade tsA3Z2c-Z1b or tsA3Z3. In addition, we found that tsAPOBEC3 proteins could be packaged into HIV-1 particles, the same as huA3G ( Fig.…”

Section: Resultssupporting

confidence: 89%

Tree Shrew Cells Transduced with Human CD4 and CCR5 Support Early Steps of HIV-1 Replication, but Viral Infectivity Is Restricted by APOBEC3

Luo

Xiang

et al. 2021

J Virol

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The host range of human immunodeficiency virus type 1 (HIV-1) is narrow. Therefore, using ordinary animal models to study HIV-1 replication, pathogenesis, and therapy is impractical. The lack of applicable animal models for HIV-1 research spurred our investigation on whether tree shrews ( Tupaia belangeri chinensis ), which are susceptible to many types of human viruses, can act as an animal model for HIV-1. Here, we report that tree shrew primary cells are refractory to wild-type HIV-1 but support the early replication steps of HIV-1 pseudotyped with the vesicular stomatitis virus glycoprotein envelope (VSV-G), which can bypass entry receptors. The exogenous expression of human CD4 renders the tree shrew cell line infectable to X4-tropic HIV-1 IIIB , suggesting that tree shrew CXCR4 is a functional HIV-1 co-receptor. However, tree shrew cells did not produce infectious HIV-1 progeny virions, even with the human CD4 receptor. Subsequently, we identified tree shrew (ts) apolipoprotein B editing catalytic polypeptide 3 (tsAPOBEC3) proteins as active inhibitors of HIV-1 particle infectivity, with virus infectivity reduced 10–1 000-fold. Unlike human APOBEC3G, the tsA3Z2c-Z1b protein was not degraded by the HIV-1 viral infectivity factor (Vif), but markedly restricted HIV-1 replication through mutagenicity and reverse transcription inhibition. The pooled knockout of tsA3Z2c-Z1b partially restored the infectivity of the HIV-1 progeny. This work suggests that tsAPOBEC3 proteins serve as an additional barrier to the development of HIV-1 tree shrew models, even when virus entry is overcome by exogenous expression of human CD4. IMPORTANCE The development of animal models is critical for studying human diseases and their pathogenesis and for evaluating drug and vaccine efficacy. For improved AIDS research, the ideal animal model of HIV-1 infection should be a small laboratory mammal that closely mimics virus replication in humans. Tree shrews exhibit considerable potential as animal models for the study of human diseases and therapeutic responses. Here, we report that human-CD4-expressing tree shrew cells support the early steps of HIV-1 replication and that tree shrew CXCR4 is a functional co-receptor of HIV-1. However, tree shrew cells harbor additional restrictions that lead to the production of HIV-1 virions with low infectivity. Thus, the tsAPOBEC3 proteins are partial barriers to developing tree shrews as an HIV-1 model. Our results provide insight into the genetic basis of HIV inhibition in tree shrews and build a foundation for the establishment of gene-edited tree shrew HIV-1-infected models.

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Section: Resultssupporting

confidence: 89%

Tree Shrew Cells Transduced with Human CD4 and CCR5 Support Early Steps of HIV-1 Replication, but Viral Infectivity Is Restricted by APOBEC3

Luo

Xiang

et al. 2021

J Virol

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“…The primer sets for this study. in the past, new host-virus relations came to be understood by through these molecules (22,23). Previously it has been reported that multiple APOBEC3 enzymes may limit the infectivity of HTLV-1 (24,25).…”

Section: Discussionmentioning

confidence: 99%

Induction of APOBEC3B cytidine deaminase in HTLV‑1‑infected humanized mice

et al. 2019

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Human T-cell leukemia virus type 1 (HTLV-1) is the causative agent of adult T-cell leukemia/lymphoma (ATL). Following viral infection with HTLV-1, certain infected cells exhibit clonal proliferation. Additional genetic and epigenetic changes in these clonally proliferating cells provide them with the selective advantage of growth, which eventually results in ATL. The precise mechanism, however, has yet to be completely elucidated. It has previously been established that APOBEC3 enzymes are potent host-antiviral restriction factors. Conversely, previous studies have reported that the A3B level is increased in tumor virus infections, such as those caused by HBV and HPV, suggesting that A3B exerts a function as a mutagen. Therefore, the present study analyzed the expression of APOBEC3 family members in various HTLV-1 infection states. No significant differences were observed in the expression between healthy donors and patients with HTLV-1-associated myelopathy. Although no significant changes in the expressions of A3C, A3D, A3F and A3G between uninfected and HTLV-1-infected mice were observed, an increased A3B expression was observed in a short-term humanized mouse model following HTLV-1 infection. In a long-term humanized mouse model following HTLV-1 infection, the gene expression array data exhibited an apparent increase in A3B and CADM1, which are indicators of ATL. Collectively, the results of the present study suggest that A3B is likely involved in the development of ATL in HTLV-1-infected humanized mice.

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“…HIV‐1 counteracts the human restriction factor A3G by expressing the Vif protein, which facilitates the proteasomal degradation of A3G by recruiting an E3 ubiquitin ligase complex, resulting in reduced encapsidation in budding virions 61 . In the results above, we have observed that DNAJB8 mediates autophagic‐lysosomal degradation of HIV‐1 Vif protein.…”

Section: Resultsmentioning

confidence: 55%

DNAJB8 facilitates autophagic‐lysosomal degradation of viral Vif protein and restricts HIV‐1 virion infectivity by rescuing APOBEC3G expression in host cells

et al. 2023

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HSP40/DNAJ family of proteins is the most diverse chaperone family, comprising about 49 isoforms in humans. Several reports have demonstrated the functional role of a few of these isoforms in the pathogenesis of various viruses, including HIV‐1. Our earlier study has shown that several isoforms of HSP40 get significantly modulated at the mRNA level during HIV‐1 infection in T cells. To explore the biological role of these significantly modulated isoforms, we analyzed their effect on HIV‐1 gene expression and virus production using knockdown and overexpression studies. Among these isoforms, DNAJA3, DNAJB1, DNAJB7, DNAJC4, DNAJC5B, DNAJC5G, DNAJC6, DNAJC22, and DNAJC30 seem to positively regulate virus replication, whereas DNAJB3, DNAJB6, DNAJB8, and DNAJC5 negatively regulate virus replication. Further investigation on the infectivity of the progeny virion demonstrated that only DNAJB8 negatively regulates the progeny virion infectivity. It was further identified that DNAJB8 protein is involved in the downregulation of Vif protein, required for the infectivity of HIV‐1 virions. DNAJB8 seems to direct Vif protein for autophagic‐lysosomal degradation, leading to rescue of the cellular restriction factor APOBEC3G from Vif‐mediated proteasomal degradation, resulting in enhanced packaging of APOBEC3G in budding virions and release of less infective progeny virion particles. Finally, our results also indicate that during the early stage of HIV‐1 infection, enhanced expression of DNAJB8 promotes the production of less infective progeny virions, but at the later stage or at the peak of infection, reduced expression of DNJAB8 protein allows the HIV‐1 to replicate and produce more infective progeny virion particles.

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HIV-1 Vif inhibits G to A hypermutations catalyzed by virus-encapsidated APOBEC3G to maintain HIV-1 infectivity

Cited by 14 publications

References 47 publications

Tree Shrew Cells Transduced with Human CD4 and CCR5 Support Early Steps of HIV-1 Replication, but Viral Infectivity Is Restricted by APOBEC3

Tree Shrew Cells Transduced with Human CD4 and CCR5 Support Early Steps of HIV-1 Replication, but Viral Infectivity Is Restricted by APOBEC3

Induction of APOBEC3B cytidine deaminase in HTLV‑1‑infected humanized mice

DNAJB8 facilitates autophagic‐lysosomal degradation of viral Vif protein and restricts HIV‐1 virion infectivity by rescuing APOBEC3G expression in host cells

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