scholarly journals Evolutionary Pattern of Asian HIV-1 Subtype B from 1990 to 2007:In SilicoAnalysis Based on Envelop Protein

2012 ◽  
Vol 2012 ◽  
pp. 1-6 ◽  
Author(s):  
Sobia Kanwal ◽  
Tariq Mahmood

HIV-1 envelop gene is a major target for vaccine development. Envelop protein and its V3 loop is shown to be important determinant of HIV-1 pathogenecity. Herein, the evolutionary pattern of most prevalent HIV-1 subtype B in Asia is determined by analyzing envelop protein and V3 domain based on the 40 randomly selected sequences of HIV-1 from database (Los Alamos), divided into four groups since 1990–2007. Construction of envelop protein phylogeny by using MEGA 5 exhibit the active mutation pattern, increase in potential N-glycosylation sites which were predicted by using online software SignalP-NN. An online available tool Drawgram was used for multiple sequence alignment (MSA) of HIV-1 subtype B envelop region and V3 loop while the alignment was rechecked by using CLUSTAL W and further was analyzed for GPGX motif and conserved region in V3 loop. Variation at fourth position of the GPGX motif and 60% conservation was found in V3 loop. Hence, this diversifying pattern of envelop protein in the Asia formulates the HIV-1 strains more pathogenic during the period of 17 years. These findings might help in understanding significant structural and functional constrains of the mutant viral strains and ultimately in vaccine development.

2021 ◽  
Vol 22 (1) ◽  
Author(s):  
Elma H. Akand ◽  
John M. Murray

Abstract Background The high variability in envelope regions of some viruses such as HIV allow the virus to establish infection and to escape subsequent immune surveillance. This variability, as well as increasing incorporation of N-linked glycosylation sites, is fundamental to this evasion. It also creates difficulties for multiple sequence alignment methods (MSA) that provide the first step in their analysis. Existing MSA tools often fail to properly align highly variable HIV envelope sequences requiring extensive manual editing that is impractical with even a moderate number of these variable sequences. Results We developed an automated library building tool NGlyAlign, that organizes similar N-linked glycosylation sites as block constraints and statistically conserved global sites as single site constraints to automatically enforce partial columns in consistency-based MSA methods such as Dialign. This combined method accurately aligns variable HIV-1 envelope sequences. We tested the method on two datasets: a set of 156 founder and chronic gp160 HIV-1 subtype B sequences as well as a set of reference sequences of gp120 in the highly variable region 1. On measures such as entropy scores, sum of pair scores, column score, and similarity heat maps, NGlyAlign+Dialign proved superior against methods such as T-Coffee, ClustalOmega, ClustalW, Praline, HIValign and Muscle. The method is scalable to large sequence sets producing accurate alignments without requiring manual editing. As well as this application to HIV, our method can be used for other highly variable glycoproteins such as hepatitis C virus envelope. Conclusions NGlyAlign is an automated tool for mapping and building glycosylation motif libraries to accurately align highly variable regions in HIV sequences. It can provide the basis for many studies reliant on single robust alignments. NGlyAlign has been developed as an open-source tool and is freely available at https://github.com/UNSW-Mathematical-Biology/NGlyAlign_v1.0 .


2010 ◽  
Vol 41 (3) ◽  
pp. 720-728 ◽  
Author(s):  
Rejane-Maria Tomasini-Grotto ◽  
Brigitte Montes ◽  
Denise Triglia ◽  
Carla Torres- Braconi ◽  
Juliana Aliano-Block ◽  
...  
Keyword(s):  
V3 Loop ◽  

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.


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.


2002 ◽  
Vol 76 (21) ◽  
pp. 10674-10684 ◽  
Author(s):  
Shan-Lu Liu ◽  
John E. Mittler ◽  
David C. Nickle ◽  
Thera M. Mulvania ◽  
Daniel Shriner ◽  
...  

ABSTRACT Although human immunodeficiency virus type 1 (HIV-1) recombinants have been found with high frequency, little is known about the forces that select for these viruses or their importance to pathogenesis. Here we document the emergence and dynamics of 11 distinct HIV-1 recombinants in a man who was infected with two subtype B HIV-1 strains and progressed rapidly to AIDS without developing substantial cellular or humoral immune responses. Although numerous frequency oscillations were observed, a single recombinant lineage eventually came to dominate the population. Numerical simulations indicate that the successive recombinant forms displaced each other too rapidly to be explained by any simple model of random genetic drift or sampling variation. All of the recombinants, including several resulting from independent recombination events, possessed the same sequence motif in the V3 loop, suggesting intense selection on this segment of the viral envelope protein. The outgrowth of the predominant V3 loop recombinants was not, however, associated with changes in coreceptor utilization. The final variant was instead notable for having lost 3 of 14 potential glycosylation sites. We also observed high ratios of synonymous-to-nonsynonymous nucleotide changes—suggestive of purifying selection—in all viral populations, with particularly high ratios in newly arising recombinants. Our study, therefore, illustrates the unusual and important patterns of viral adaptation that can occur in a patient with weak immune responses. Although it is hard to tease apart cause and effect in a single patient, the correlation with disease progression in this patient suggests that recombination between divergent viruses, with its ability to create chimeras with increased fitness, can accelerate progression to AIDS.


Author(s):  
Marleen Vanden Haesevelde ◽  
Robert J. DeLeys ◽  
Anja Van Geel ◽  
Bart Vanderborght ◽  
Morais de Sá ◽  
...  
Keyword(s):  
V3 Loop ◽  

2009 ◽  
Vol 4 (6) ◽  
pp. 237-241 ◽  
Author(s):  
Abraham Joseph Kandathil ◽  
Rajesh Kannangai ◽  
Oriapadickal Cherian Abraham ◽  
Susanne Alexander Pulimood ◽  
Gopalan Sridharan

1996 ◽  
Vol 91 (3) ◽  
pp. 339-342 ◽  
Author(s):  
MG Morgado ◽  
ML Guimarães ◽  
CBG Gripp ◽  
I Neves Jr ◽  
CI Costa ◽  
...  
Keyword(s):  
V3 Loop ◽  

2020 ◽  
Vol 10 (1) ◽  
Author(s):  
Maxime Beretta ◽  
Julie Migraine ◽  
Alain Moreau ◽  
Asma Essat ◽  
Cécile Goujard ◽  
...  

Abstract The diversity of the HIV-1 envelope glycoproteins (Env) is largely a consequence of the pressure exerted by the adaptive immune response to infection. While it was generally assumed that the neutralizing antibody (NAb) response depended mainly on the infected individual, the concept that virus-related factors could be important in inducing this response has recently emerged. Here, we analyzed the influence of the infecting viral strain in shaping NAb responses in four HIV-1 infected subjects belonging to a transmission chain. We also explored the impact of NAb responses on the functional evolution of the viral quasispecies. The four patients developed a strong autologous neutralizing antibody response that drove viral escape and coincided with a parallel evolution of their infecting quasispecies towards increasing infectious properties, increasing susceptibility to T20 and increasing resistance to both CD4 analogs and V3 loop-directed NAbs. This evolution was associated with identical Env sequence changes at several positions in the V3 loop, the fusion peptide and the HR2 domain of gp41. The common evolutionary pattern of Env in different hosts suggests that the capacity of a given Env to adapt to changing environments may be restricted by functional constraints that limit its evolutionary landscape.


2011 ◽  
Vol 9 (8) ◽  
pp. 636-641 ◽  
Author(s):  
Hai-Zhou Zhou ◽  
Hua-Feng Xu ◽  
Xiao-Min Xin ◽  
Xiu-Ru Guan ◽  
Jin Zhou

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