Molecular Modeling of Subtype-Specific Tat Protein Signatures to Predict Tat-TAR Interactions That May Be Involved in HIV-Associated Neurocognitive Disorders.
Abstract: In this study, we attempted to understand the molecular mechanism by which Tat subtype-specific variation, particularly, C31S, R57S, and Q63E influence the Tat-TAR interaction.
Abstract: Subtype-specific Tat protein signatures including C31S, R57S and Q63E present in Tat subtype C has previously been linked to a lowered neuropathophysiology compared to Tat subtype B.
Introduct
Discussion: These included the C31S, R57S, and Q63E in Tat subtype C.
HIV-1C and HIV-1B Tat protein polymorphism in Southern Brazil.
Abstract: The frequency of C31S and other key point mutations in HIV-1 Tat C in Brazil were similar to those described in Africa, although lower than those in India.
Abstract: The frequency of C31S substitution on HIV-1 Tat C in Brazil was 82% vs.
The Signature Amino Acid Residue Serine 31 of HIV-1C Tat Potentiates an Activated Phenotype in Endothelial Cells.
Abstract: The natural cysteine to serine variation at position 31 of Tat in HIV-1C disrupts the dicysteine motif attenuating the chemokine function of Tat.
Introduction: Several previous reports, including from our laboratory, suggested a neuroprotective function for the natural polymorphism of C31>S in HIV-1C Tat.
Introduction: The results from the study suggested that the C31S substitution does not confer decreased impairment in cognitive performance.
Discussion: It would be necessary to understand if the natural variation of C31S in HIV-1C Tat, leading to significantly enhanced induction of CCL2 production, is a compensatory mechanism for the differences in the basic domain and the RGD motif.
A Naturally Occurring Polymorphism in the HIV-1 Tat Basic Domain Inhibits Uptake by Bystander Cells and Leads to Reduced Neuroinflammation.
Introduction: We and others have shown that a naturally occurring polymorphism in Tat, a cysteine to serine substitution at residue 31 (C31S) significantly reduces its neuropathogenic potential, diminishing Tat's ability to recruit MPs, its neurotoxicity and its pro-inflammatory function.
Discussion: We have reported a naturally occurring C31S polymorphism in Tat dicysteine motif in HIV-1C, which is considered to be important for monocyte chemotaxis function - a property that may underlie the increased monocyte infiltration in CNS that is a hallmark of HAD.
Neuroimaging abnormalities in clade C HIV are independent of Tat genetic diversity.
Result: Results of the MANCOVA revealed no significant differences between the C31S and C31C groups on the volumetric variables (Wilk's Lambda = 0.97, F(6,120) = 0.52, p = 0.78).
Result: Results of the MANOVAs revealed no significant differences between the C31S and C31C groups on the DTI metrics for the CC (Wilk's Lambda = 0.967
Discussion: Specifically, while the frequency of C31S was less than 5% in samples from India, the frequency increased to more than 25% in samples from South Africa.
Discussion: While most of these investigations did not sequence the dicysteine motif of Tat to confirm the presence of cysteine or serine at position 31, the results are consistent with our previous cognitive study in which C31S status was defined.
Molecular and Genetic Characterization of HIV-1 Tat Exon-1 Gene from Cameroon Shows Conserved Tat HLA-Binding Epitopes: Functional Implications.
Result: Mutations identified in the Tat cysteine-rich region included N29K and N36I in CRF02_AG and CRF11_cpx viral isolates, respectively (Figure 3A,B); N23T, N24K, and K29T in subtype-G isolates (Figure 3C); N23T and T24K in CRF13_cpx (Figure 3D); K24S, Y26H, and K29H in subtype-D (Figure 3E); N24K and F26W in CRF22_01A1 (Figure 3F); K24Q, C31S, and P35Q in CRF18_cpx (Figure 3G); and N23S and PMID: 27473196
2016
Journal of neurovirology
Abstract: With respect to the effect of HIV-1 subtype diversity, analyses of HIV-1 clade C infection among South Africans revealed that clade C infection induced cognitive impairment that was independent of the substitution in HIV-1 Trans-Activator of Transcription (Tat; C31S).
Introduction:
Introduction: Paul identified significant impairments in cognitive function in HIV-positive individuals compared to HIV-negative individuals independent of the Tat mutation (C31S).
Discussion: HIV-1 clade C infection in South Africa revealed significant functional cognitive impairment that was independent of Tat (C31S) mutation, suggesting thereby that HIV-1 clade C could cause cognitive impairment similar to other HIV clades.
The gp120 protein is a second determinant of decreased neurovirulence of Indian HIV-1C isolates compared to southern African HIV-1C isolates.
Abstract: We previously demonstrated that a C31S substitution in Clade-C Tat dicysteine motif reduces monocyte recruitment, cytokine induction and direct neurotoxicity.
Abstract: We previously reported on the genotypic differences in Tat protein between clade-C and rest of the clades showing that approximately 90% of clade-C HIV-1 Tat sequences worldwide contained this C31S polymorphism, while 99% of non-clade C isolates lacked this Tat polymorphism at C31 residue (Ranga et al.
Discussion: The premise of those studies has been that the decreased monocyte migration caused by C31S<
Discussion: Therefore, until now, the decreased neurovirulence of HIV-1C has been primarily attributed to C31S polymorphism.
Impact of the HIV Tat C30C31S dicysteine substitution on neuropsychological function in patients with clade C disease.
Introduction: The C31S substitution resulted in reduced monocyte chemotaxis, and was referenced as a potential biological explanation for the lower incidence of HAD reported in clade C.
Introduction: The present study examined this important question among patients infected with clade C inclusive with or without the C31S Tat substitution.
Introduction: These results help to explain the high level of cognitive impairment and neuroimaging abnormalities in South Africa but the findings do not explain the high rate of cognitive impairment previously reported in India where the C31S substitution is present in more than 90 percent of cases.
Introduction: To date
Method: Nucleotide sequences were translated into amino acid sequences and the C30C31 motif or C31S mutation for each patient was noted.
Differential induction of interleukin-10 in monocytes by HIV-1 clade B and clade C Tat proteins.
PMID: 20378550
2010
The Journal of biological chemistry
Abstract: Additionally, the C31S mutation found in C Tat is responsible for the inability of these Tat proteins to produce high IL-10 levels in monocytes due to its inability to induce intracellular calcium flux through L-type calcium channels.
Abstract: In this study, we show that the cysteine to serine mutation at position 31, found in >90% of HIV-1 clade C Tat proteins, results in a marked decrease in IL-10 production in monocytes compared with clade B Tat.
HIV mutation literature information.
PMID: 
2022
Frontiers in microbiology
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