Paradigm development: Comparative and predictive 3D modeling of HIV-1 Virion Infectivity Factor (vif)

Balaji, S.; Kalpana, Rangaswamy; Shapshak, Paul

doi:10.6026/97320630001290

Cited by 19 publications

(13 citation statements)

References 47 publications

(57 reference statements)

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Notably, most combinations of amino acids in these epistatic sites tend to be associated with CD4+ T cell counts below 500 cells per mm 3 (see Figure 2 for a detailed description of pairs of residues and their correlation with CD4 counts). We used a proposed three-dimensional computational model of Vif [32] (PDB: 1VZF) to shown the location of the pairs of epistatic codons on the structure of this viral protein (Figure 3). …”

Section: Resultsmentioning

confidence: 99%

“…These sites under positive selection were exactly the same as those detected in the recombination-free data (open diamonds in the Figure 3). Mapping positively selected sites in the Vif protein sequence and in the 3D structure of a computational model of Vif protein [32] (PDB: 1VZF), revealed they were concentrated between the 21 WKSLVK 26 and 40 YRHHY 44 motif ( i.e ., 31, 33, 37, 39 and 47), both important to Vif-induced degradation of A3G/F complexes. It is important to mention that the N-terminal region of Vif protein binds selectively to HIV-1 genomic RNA [35] and mRNA of A3G [36].…”

Section: Resultsmentioning

confidence: 99%

See 1 more Smart Citation

Codon pairs of the HIV-1 vif gene correlate with CD4+ T cell count

et al. 2013

View full text Add to dashboard Cite

BackgroundThe human APOBEC3G (A3G) protein activity is associated with innate immunity against HIV-1 by inducing high rates of guanosines to adenosines (G-to-A) mutations (viz., hypermutation) in the viral DNA. If hypermutation is not enough to disrupt the reading frames of viral genes, it may likely increase the HIV-1 diversity. To counteract host innate immunity HIV-1 encodes the Vif protein that binds A3G protein and form complexes to be degraded by cellular proteolysis.MethodsHere we studied the pattern of substitutions in the vif gene and its association with clinical status of HIV-1 infected individuals. To perform the study, unique vif gene sequences were generated from 400 antiretroviral-naïve individuals.ResultsThe codon pairs: 78–154, 85–154, 101–157, 105–157, and 105–176 of vif gene were associated with CD4+ T cell count lower than 500 cells per mm3. Some of these codons were located in the 81LGQGVSIEW89 region and within the BC-Box. We also identified codons under positive selection clustered in the N-terminal region of Vif protein, between 21WKSLVK26 and 40YRHHY44 regions (i.e., 31, 33, 37, 39), within the BC-Box (i.e., 155, 159) and the Cullin5-Box (i.e., 168) of vif gene. All these regions are involved in the Vif-induced degradation of A3G/F complexes and the N-terminal of Vif protein binds to viral and cellular RNA.ConclusionsAdaptive evolution of vif gene was mostly to optimize viral RNA binding and A3G/F recognition. Additionally, since there is not a fully resolved structure of the Vif protein, codon pairs associated with CD4+ T cell count may elucidate key regions that interact with host cell factors. Here we identified and discriminated codons under positive selection and codons under functional constraint in the vif gene of HIV-1.

show abstract

Section: Resultsmentioning

confidence: 99%

Section: Resultsmentioning

confidence: 99%

Codon pairs of the HIV-1 vif gene correlate with CD4+ T cell count

et al. 2013

View full text Add to dashboard Cite

show abstract

“…Two laboratories have predicted a structure of Vif through computational methods involving comparative modelling of Vif relative to known structural folds in the Protein Database [ 34 , 35 ]. Although the groups used different clades of HIV-1 Vif for modelling, the amino acid sequence immediately flanking and including the dimerization domain (KPPLPSV) and PPLP alone had a similar predicted structure (root mean square deviation of 2.91 Å and 2.49 Å, respectively; personal communication, David H. Mathews).…”

Section: Introductionmentioning

confidence: 99%

The dimerization domain of HIV-1 viral infectivity factor Vif is required to block virion incorporation of APOBEC3G

Miller

Presnyak²,

Smith

2007

Retrovirology

View full text Add to dashboard Cite

Background: The HIV-1 accessory protein known as viral infectivity factor or Vif binds to the host defence factor human APOBEC3G (hA3G) and prevents its assembly with viral particles and mediates its elimination through ubiquitination and degradation by the proteosomal pathway. In the absence of Vif, hA3G becomes incorporated within viral particles. During the post entry phase of infection, hA3G attenuates viral replication by binding to the viral RNA genome and deaminating deoxycytidines to form deoxyuridines within single stranded DNA regions of the replicated viral genome. Vif dimerization has been reported to be essential for viral infectivity but the mechanistic requirement for Vif multimerization is unknown.

show abstract

“…Until this date, several regions in Vif and A3G have been mapped, and the effect on their interaction was studied. Nevertheless, the threedimensional molecular structure of both proteins has not yet been determined, and only theoretical predictions providing structural information on Vif domains are available (Auclair et al 2007;Balaji et al 2006;Barraud et al 2008;Huthoff and Malim 2007;Lv et al 2007;Zhang et al 2008).…”

Section: Discussionmentioning

confidence: 99%

HIV-1 Vif Interaction with APOBEC3 Deaminases and its Characterization by a New Sensitive Assay

Cadima-Couto

Saraiva

Santos

et al. 2011

J Neuroimmune Pharmacol

View full text Add to dashboard Cite

The human APOBEC3 (A3) cytidine deaminases, such as APOBEC3G (A3G) and APOBEC3F (A3F), are potent inhibitors of Vif-deficient human immunodeficiency virus type 1 (HIV-1). HIV-1 Vif (viral infectivity factor) binds A3 proteins and targets these proteins for ubiquitination and proteasomal degradation. As such, the therapeutic blockage of Vif-A3 interaction is predicted to stimulate natural antiviral activity by rescuing APOBEC expression and virion packaging. In this study, we describe a successful application of the Protein Fragment Complementation Assay (PCA) based on the enzyme TEM-1 β-lactamase to study Vif-A3 interactions. PCA is based on the interaction between two protein binding partners (e.g., Vif and A3G), which are fused to the two halves of a dissected marker protein (β-lactamase). Binding of the two partners reassembles β-lactamase and hence reconstitutes its activity. To validate our assay, we studied the effect of well-described Vif (DRMR, YRHHY) and A3G (D128K) mutations on the interaction between the two proteins. Additionally, we studied the interaction of human Vif with other members of the A3 family: A3F and APOBEC3C (A3C). Our results demonstrate the applicability of PCA as a simple and reliable technique for the assessment of Vif-A3 interactions. Furthermore, when compared with co-immunoprecipitation assays, PCA appeared to be a more sensitive technique for the quantitative assessment of Vif-A3 interactions. Thus, with our results, we conclude that PCA could be used to quantitatively study specific domains that may be involved in the interaction between Vif and APOBEC proteins.

show abstract

Paradigm development: Comparative and predictive 3D modeling of HIV-1 Virion Infectivity Factor (vif)

Cited by 19 publications

References 47 publications

Codon pairs of the HIV-1 vif gene correlate with CD4+ T cell count

Codon pairs of the HIV-1 vif gene correlate with CD4+ T cell count

The dimerization domain of HIV-1 viral infectivity factor Vif is required to block virion incorporation of APOBEC3G

HIV-1 Vif Interaction with APOBEC3 Deaminases and its Characterization by a New Sensitive Assay

Contact Info

Product

Resources

About