APOBEC3G genetic variants and their association with risk of HIV infection in highly exposed Caucasians

Valcke, Han Sang; Bernard, Nicole F.; Bruneau, Julie; Alary, Michel; Tsoukas, Christos; Roger, Michel

doi:10.1097/01.aids.0000247124.35129.e1

Cited by 47 publications

(37 citation statements)

References 12 publications

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“…Such variation could be provided through differences in A3G and/or A3F or Vif protein sequences, expression levels, or regulation of protein function. Indeed, a single nucleotide polymorphism in A3G that encodes the H186R change has been associated with an accelerated progression of HIV-1 disease in African Americans (1), a noncoding polymorphism in intron 4 of A3G has been associated with an increased risk of infection in Caucasians (79), and a polymorphism in CUL5 (which encodes cullin 5) has been linked to more rapid disease progression (2). Conversely, another study was unable to find an association between the H186R or other A3G polymorphisms and disease progression (22).…”

mentioning

confidence: 99%

Defining APOBEC3 Expression Patterns in Human Tissues and Hematopoietic Cell Subsets

Koning

Newman

Kim

et al. 2009

J Virol

304

352

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Human APOBEC3 enzymes are cellular DNA cytidine deaminases that inhibit and/or mutate a variety of retroviruses, retrotransposons, and DNA viruses. Here, we report a detailed examination of human APOBEC3 gene expression, focusing on APOBEC3G (A3G) and APOBEC3F (A3F), which are potent inhibitors of human immunodeficiency virus type 1 (HIV-1) infection but are suppressed by HIV-1 Vif. A3G and A3F are expressed widely in hematopoietic cell populations, including T cells, B cells, and myeloid cells, as well as in tissues where mRNA levels broadly correlate with the lymphoid cell content (gonadal tissues are exceptions). By measuring mRNA copy numbers, we find that A3G mRNA is ϳ10-fold more abundant than A3F mRNA, implying that A3G is the more significant anti-HIV-1 factor in vivo. A3G and A3F levels also vary between donors, and these differences are sustained over 12 months. Responses to T-cell activation or cytokines reveal that A3G and A3F mRNA levels are induced ϳ10-fold in macrophages and dendritic cells (DCs) by alpha interferon (IFN-␣) and ϳ4-fold in naïve CD4 ؉ T cells. However, immunoblotting revealed that A3G protein levels are induced by IFN-␣ in macrophages and DCs but not in T cells. In contrast, T-cell activation and IFN-␥ had a minimal impact on A3G or A3F expression. Finally, we noted that A3A mRNA expression and protein expression are exquisitely sensitive to IFN-␣ induction in CD4 ؉ T cells, macrophages, and DCs but not to T-cell activation or other cytokines. Given that A3A does not affect HIV-1 infection, these observations imply that this protein may participate in early antiviral innate immune responses.

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mentioning

confidence: 99%

Defining APOBEC3 Expression Patterns in Human Tissues and Hematopoietic Cell Subsets

Koning

Newman

Kim

et al. 2009

J Virol

304

352

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“…Additionally, when transfected at high levels, A3 proteins are able to overwhelm matched-host Vif, resulting in a virus restriction phenotype compared to the phenotype seen with normal A3 expression (55,59,61,62). In a clinical setting, polymorphisms in human A3 genes have been associated with the risk of HIV acquisition (102)(103)(104) and with HIV disease progression (102,105). Likewise, several reports have found that higher levels of A3 expression are associated with lower HIV loads (106,107) and resistance to infection (108,109).…”

Section: Discussionmentioning

confidence: 99%

Accessory Genes Confer a High Replication Rate to Virulent Feline Immunodeficiency Virus

Troyer

Thompson

Elder

et al. 2013

J Virol

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“…The KIR 3DS1 allele on NK cells is associated with protection from infection, especially in combination with certain HLA alleles (HLA Bw4-80I, including HLA B*57), which serve as ligands for KIR3DS1 [77]. Furthermore, polymorphisms within genes coding for intracellular restriction factors like Trim5a, PPIA and APOBEC3G have also been reported to affect the susceptibility to HIV-1 infection [78][79][80][81][82][83][84].…”

Section: Genetic Host Factors Influencing Hiv-1 Acquisitionmentioning

confidence: 99%

HIV-1 Transmission and Viral Adaptation to the Host

Gijsbers

Schuitemaker

Kootstra³

2011

Future Virol.

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HIV-1 transmission predominantly occurs via mucosal transmission and blood–blood contact. In most newly infected individuals, outgrowth of a single virus variant has been described. This indicates that HIV-1 transmission is a very inefficient process and is restricted by an extensive transmission bottleneck. The transmission rate is directly correlated to the viral load in the donor and the susceptibility of the recipient, which is influenced by factors such as the integrity of mucosal barriers, target cell availability and genetic host factors. After establishment of infection in the new host, the viral population remains very homogenous until the host immune response drives evolution of the viral quasispecies. This review describes our current knowledge on HIV-1 transmission and recent insights in viral adaption to its host.

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APOBEC3G genetic variants and their association with risk of HIV infection in highly exposed Caucasians

Cited by 47 publications

References 12 publications

Defining APOBEC3 Expression Patterns in Human Tissues and Hematopoietic Cell Subsets

Defining APOBEC3 Expression Patterns in Human Tissues and Hematopoietic Cell Subsets

Accessory Genes Confer a High Replication Rate to Virulent Feline Immunodeficiency Virus

HIV-1 Transmission and Viral Adaptation to the Host

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