2012
DOI: 10.1128/jvi.06082-11
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The Activity Spectrum of Vif from Multiple HIV-1 Subtypes against APOBEC3G, APOBEC3F, and APOBEC3H

Abstract: The APOBEC3 family comprises seven cytidine deaminases (APOBEC3A [A3A] to A3H), which are expressed to various degrees in HIV-1 susceptible cells. The HIV-1 Vif protein counteracts APOBEC3 restriction by mediating its degradation by the proteasome. We hypothesized that Vif proteins from various HIV-1 subtypes differ in their abilities to counteract different APOBEC3 proteins. Seventeen Vif alleles from seven HIV-1 subtypes were tested for their abilities to degrade and counteract A3G, A3F, and A3H haplotype II… Show more

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Cited by 89 publications
(124 citation statements)
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“…In addition, we identified a region important for A3H-hapII neutralization that is not required for A3F or A3G neutralization. Studies conducted by us and others have determined that Vif1 also has distinct regions for the neutralization of A3F, A3G, and A3H-hapII (34)(35)(36)(37)(38)(39). It is important to point out that it cannot be concluded that these motifs that have been identified to be critical for interaction through mutational analyses are themselves directly involved in the protein-protein interactions.…”
Section: Discussionmentioning
confidence: 97%
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“…In addition, we identified a region important for A3H-hapII neutralization that is not required for A3F or A3G neutralization. Studies conducted by us and others have determined that Vif1 also has distinct regions for the neutralization of A3F, A3G, and A3H-hapII (34)(35)(36)(37)(38)(39). It is important to point out that it cannot be concluded that these motifs that have been identified to be critical for interaction through mutational analyses are themselves directly involved in the protein-protein interactions.…”
Section: Discussionmentioning
confidence: 97%
“…Our results also indicate that A3H-hapII is efficiently degraded by the Vif2 used in our studies (derived from HIV-2 ROD12 ). Because A3H-hapII sensitivity to Vif1 is dependent on the subtype from which Vif1 is derived (35,72), it would be interesting to determine whether A3H-hapII is sensitive to other Vif2 variants as well.…”
Section: Discussionmentioning
confidence: 99%
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“…We generated a panel of 13 Vif mutants consisting of positively charged arginine and negatively charged glutamate at and around positions deemed important for A3H recognition based on previous work (Fig. 5A) (12)(13)(14)(15)(16) and tested their activity against selected Vif-resistant A3H mutants in single-cycle infectivity assays. We found that Vif-WT, Vif-G37R, and Vif-D61R efficiently counteracted A3H-WT, Vif mutants G37E, G60E, A62E, A62R, R63E, and R90E showed reduced anti-A3H activity, and Vif mutants F39E, F39R, E54R, H56E, and R93E completely lost their activity against A3H-WT (Fig.…”
Section: Identification Of the Vif Binding Site Of A3hmentioning
confidence: 99%
“…To date, only a single amino acid at position 121 in A3H has been implicated in the interaction with HIV Vif: mutating aspartic acid (D) at position 121 to a lysine (K) renders A3H resistant to Vif (14,15). On the Vif side, amino acid positions 39, 48, and 60 to 63 are important for the counteraction of A3H, indicating they are part of the A3H binding site (12,13,15,16).…”
mentioning
confidence: 99%