scholarly journals Amino acid sequence divergence of Tat protein (exon1) of subtype B and C HIV-1 strains: Does it have implications for vaccine development?

2009 ◽  
Vol 4 (6) ◽  
pp. 237-241 ◽  
Author(s):  
Abraham Joseph Kandathil ◽  
Rajesh Kannangai ◽  
Oriapadickal Cherian Abraham ◽  
Susanne Alexander Pulimood ◽  
Gopalan Sridharan
1992 ◽  
Vol 40 (3) ◽  
pp. 313 ◽  
Author(s):  
PR Baverstock ◽  
L Christidis ◽  
M Krieg ◽  
J Birrell

A number of lines of evidence suggest that the rate of molecular evolution in birds is slower than in other vertebrates. This hypothesis was tested by measuring the extent of amino-acid sequence divergence in albumin among species of parrots by means of microcomplement fixation. This group was chosen because its modern distribution is strongly suggestive of a Gondwanan origin. The results show that the intercontinental albumin distances are well below those expected for a Gondwanan group. These data are in accord with the hypothesis that birds have a slower rate of molecular evolution, although other explanations are possible.


2020 ◽  
Vol 21 (8) ◽  
pp. 2910 ◽  
Author(s):  
Wen-Hung Wang ◽  
Chun-Sheng Yeh ◽  
Chih-Yen Lin ◽  
Ruei-Yu Yuan ◽  
Aspiro Nayim Urbina ◽  
...  

HIV-1 CRF07_BC is a recombinant virus with amino acid (a.a.) deletions in p6Gag, which are overlapped with the Alix-binding domain. Galectin-3 (Gal3), a β-galactose binding lectin, has been reported to interact with Alix and regulate HIV-1 subtype B budding. This study aims to evaluate the role of Gal3 in HIV-1 CRF07_BC infection and the potential effect of a.a. deletions on Gal3-mediated regulation. A total of 38 HIV-1+ injecting drug users (IDUs) were enrolled in the study. Viral characterization and correlation of Gal3 were validated. CRF07_BC containing 7 a.a. deletions and wild-type in the p6Gag (CRF07_BC-7d and -wt) were isolated and infectious clones were generated. Viral growth kinetic and budding assays using Jurkat-CCR5/Jurkat-CCR5-Gal3 cells infected with CRF07_BC were performed. Results indicate that 69.4% (25/38) of the recruited patients were identified as CRF07_BC, and CRF07_BC-7d was predominant. Slow disease progression and significantly higher plasma Gal3 were noted in CRF07_BC patients (p < 0.01). Results revealed that CRF07_BC infection resulted in Gal3 expression, which was induced by Tat. Growth dynamic and budding assays indicated that Gal3 expression in Jurkat-CCR5 cells significantly enhanced CRF07_BC-wt replication and budding (p < 0.05), while the promoting effect was ameliorated in CRF07_BC-7d. Co-immunoprecipitation found that deletions in the p6Gag reduced Gal-3-mediated enhancement of the Alix–Gag interaction.


1996 ◽  
Vol 70 (9) ◽  
pp. 931-937
Author(s):  
Shunji MATSUDA ◽  
Masahiro NODA ◽  
Akie TOYOTA ◽  
Shizuyo TOKUMOTO ◽  
Masahiko MIYATA

2010 ◽  
Vol 84 (23) ◽  
pp. 12437-12444 ◽  
Author(s):  
Elizabeth G. Ryland ◽  
Yanhua Tang ◽  
Celia D. Christie ◽  
Margaret E. Feeney

ABSTRACT The genetic heterogeneity of HIV-1 poses a major obstacle to vaccine development. Although most horizontally acquired HIV-1 infections are initiated by a single homogeneous virus, marked genetic diversification and evolution occur following transmission. The relative contribution of the antiviral immune response to intrahost viral evolution remains controversial, in part because the sequence of the transmitted virus and the array of T-cell epitopes targeted by both donor and recipient are seldom known. We directly compared predominant viral sequences derived from 52 mother-child transmission pairs following vertical infection and identified 1,475 sites of mother-infant amino acid divergence within Nef, Gag, and Pol. The cumulative number of mutations away from the consensus subtype B sequence increased linearly with time since transmission, whereas reversions toward the consensus sequence accumulated more slowly with increasing duration of infection. Comprehensive mapping of T-cell epitopes targeted by these mothers and infants revealed that 14% of nonsynonymous mutations away from the consensus sequence were located within regions targeted by the infant, whereas 24% of nonsynonymous mutations toward the consensus sequence were located in regions targeted by the mother. On the basis of analysis of optimal epitopes listed in the HIV Molecular Immunology Database, fewer than 10% of epitopes containing maternal escape mutations reverted to the consensus sequence following transmission to an infant lacking the restricting HLA allele. This surprisingly low reversion rate of mutated epitopes following transmission suggests that the fitness cost associated with many CD8 epitope mutations may be modest.


AIDS ◽  
2000 ◽  
Vol 14 (18) ◽  
pp. 2937-2939 ◽  
Author(s):  
Daniel R. Briggs ◽  
Daniel L. Tuttle ◽  
John W. Sleasman ◽  
Maureen M. Goodenow

2005 ◽  
Vol 79 (2) ◽  
pp. 1154-1163 ◽  
Author(s):  
Feng Gao ◽  
Eric A. Weaver ◽  
Zhongjing Lu ◽  
Yingying Li ◽  
Hua-Xin Liao ◽  
...  

ABSTRACT Genetic variation of human immunodeficiency virus (HIV-1) represents a major obstacle for AIDS vaccine development. To decrease the genetic distances between candidate immunogens and field virus strains, we have designed and synthesized an artificial group M consensus env gene (CON6 gene) to be equidistant from contemporary HIV-1 subtypes and recombinants. This novel envelope gene expresses a glycoprotein that binds soluble CD4, utilizes CCR5 but not CXCR4 as a coreceptor, and mediates HIV-1 entry. Key linear, conformational, and glycan-dependent monoclonal antibody epitopes are preserved in CON6, and the glycoprotein is recognized equally well by sera from individuals infected with different HIV-1 subtypes. When used as a DNA vaccine followed by a recombinant vaccinia virus boost in BALB/c mice, CON6 env gp120 and gp140CF elicited gamma interferon-producing T-cell responses that recognized epitopes within overlapping peptide pools from three HIV-1 Env proteins, CON6, MN (subtype B), and Chn19 (subtype C). Sera from guinea pigs immunized with recombinant CON6 Env gp120 and gp140CF glycoproteins weakly neutralized selected HIV-1 primary isolates. Thus, the computer-generated “consensus” env genes are capable of expressing envelope glycoproteins that retain the structural, functional, and immunogenic properties of wild-type HIV-1 envelopes.


2020 ◽  
Author(s):  
Zetao Cheng ◽  
Sherimay D. Ablan ◽  
Eric O. Freed ◽  
Haiying Wang ◽  
Shixing Tang

Abstract Background We previously observed that individuals infected with HIV-1 CRF07_BC showed slower disease progression than those infected with HIV-1 subtype B or CRF01_AE. CRF07_BC viruses carry two unique mutations in the p6 Gag protein: insertion of PTAPPE sequences downstream of the original Tsg101 binding domain, and deletion of a seven-amino-acid sequence ( 30 PIDKELY 36 ) that partially overlaps with the Alix binding domain. To further define the role of these mutations in virus release and replication, we introduced them into the HIV-1 proviral clone pNL4-3 for functional characterization. Results We found that the seven-amino-acid deletion, but not the PTAPPE insertion, significantly decreased virus release, Gag processing, and virus infectivity. The seven-amino-acid deletion also resulted in a virus replication defect in both T-cell lines and peripheral blood mononuclear cells. We found that these defects were caused by the seven-amino-acid deletion in p6 Gag , especially deletion of Tyr-36 of p6 Gag , not the deletion of the overlapping p6* sequence in the HIV-1 GagPol protein. The p6 Gag deletion mutant was resistant to a dominant-negative Alix fragment, suggesting a loss of binding between p6 Gag and Alix. Conclusions Our results indicate that the patient-derived seven-amino-acid deletion in p6 Gag of HIV-1 CRF07_BC virus affects virus release, infectivity and replication capacity by disrupting the interaction between HIV-1 p6 Gag and host protein Alix. These results may explain the slower disease progression observed in the subjects infected with HIV-1 CRF07_BC bearing this unique mutation.


1998 ◽  
Vol 72 (7) ◽  
pp. 5831-5839 ◽  
Author(s):  
Laurent Bélec ◽  
Ali Si Mohamed ◽  
Michaela C. Müller-Trutwin ◽  
Jacques Gilquin ◽  
Laurent Gutmann ◽  
...  

ABSTRACT A small number of cases of human immunodeficiency virus (HIV) infection have been reported in individuals with no identified risk factors for transmission. We report on the seroconversion of the 61-year-old mother and the subsequent finding of HIV seropositivity in the 66-year-old father of a 31-year-old AIDS patient. Extensive investigation failed to identify any risk factor for intrafamilial transmission. We conducted a genetic analysis and determined the amino acid signature patterns of the V3, V4, and V5 hypervariable domains and flanking regions in the HIV-1 gp120 env gene of 26 clones derived from proviral DNA in peripheral blood mononuclear cells of the members of the family. env sequences of the viruses isolated from the patients were compared with sequences of HIV-1 subtype B viruses from Europe and local field isolates. Phylogenetic analysis revealed that the sequences of the viruses isolated from the patients were genetically related and formed an intrafamilial cluster of HIV-1 distinct from other subtype B viruses. Interindividual nucleotide variability in the C2-V3 and V4-C4-V5 domains ranged between 1.2 and 5.0% and between 2.2 and 7.5%, respectively, whereas divergence between HIV strains from the patients and control viral strains ranged from 6.6 to 29.3%. The amino acid signature patterns of viral clones from the three patients were closely related. In the C2-V3 region, two minor clones derived from the son’s virus showed less nucleotide divergence (mean, 3.5 and 3.9%) than did the clones derived from the viruses of both parents or the seven other predominant clones derived from the virus from the son (mean, 5.4%). The top of the V3 loop of the last two clones and of all viral clones from the parents exhibited an unusual GPGG sequence. This is the first report of genotypic relatedness of HIV-1 in three adults of the same family in the absence of identified risk factor for transmission between the members of the family. Our findings suggest that atypical transmission of HIV may occur.


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