Identification of a Region within the Cytoplasmic Domain of the Subtype B Vpu Protein of Human Immunodeficiency Virus Type 1 (HIV-1) That Is Responsible for Retention in the Golgi Complex and Its Absence in the Vpu Protein from a Subtype C HIV-1

2005 ◽  
Vol 21 (5) ◽  
pp. 379-394 ◽  
Author(s):  
Erik Pacyniak ◽  
Melissa L. Gomez ◽  
Lisa M. Gomez ◽  
Ellyn R. Mulcahy ◽  
Mollie Jackson ◽  
...  
Keyword(s):  
Human Immunodeficiency Virus ◽  
Human Immunodeficiency Virus Type ◽  
Virus Type ◽  
Golgi Complex ◽  
Cytoplasmic Domain ◽  
Subtype C ◽  
Subtype B ◽  
Immunodeficiency Virus ◽  
Hiv 1

scholarly journals A Recent Outbreak of Human Immunodeficiency Virus Type 1 Infection in Southern China Was Initiated by Two Highly Homogeneous, Geographically Separated Strains, Circulating Recombinant Form AE and a Novel BC Recombinant

2000 ◽  
Vol 74 (23) ◽  
pp. 11286-11295 ◽  
Author(s):  
Sucheep Piyasirisilp ◽  
Francine E. McCutchan ◽  
Jean K. Carr ◽  
Eric Sanders-Buell ◽  
Wei Liu ◽  
...  
Keyword(s):  
Human Immunodeficiency Virus ◽  
Human Immunodeficiency Virus Type ◽  
Virus Type ◽  
Southern China ◽  
Recombinant Form ◽  
Subtype C ◽  
Subtype B ◽  
Immunodeficiency Virus ◽  
Hiv 1

ABSTRACT New outbreaks of human immunodeficiency virus type 1 (HIV-1) among injecting drug users (IDUs) are spreading in China along heroin trafficking routes. Recently, two separate HIV-1 epidemics among IDUs were reported in Guangxi, Southern China, where partial sequencing of the env gene showed subtype C and circulating recombinant form (CRF) AE. We evaluated five virtually full-length HIV-1 genome sequences from IDUs in Guangxi to determine the genetic diversity and the presence of intersubtype recombinants. Sequence analysis showed two geographically separated, highly homogeneous HIV-1 strains. B/C intersubtype recombinants were found in three IDUs from Baise City, in a mountainous region near the Yunnan-Guangxi border. These were mostly subtype C, with portions of the capsid and reverse transcriptase (RT) genes from subtype B. The subtype B portion of the capsid was located in the N-terminal domain, which has been shown to influence virus core maturation, virus infectivity, and binding to cyclophilin A, whereas the subtype B portion of RT was located in the palm subdomain, which is the active site of the enzyme. These BC recombinants differed from a BC recombinant found in Xinjiang Province in northwestern China. CRF AE strains were found in IDUs from Nanning, the capital of Guangxi, and in IDUs from Pingxiang City near the China-Vietnam border. The AE and BC recombinants were both remarkable for their low interpatient diversity, less than 1% for the full genome. Rapid spread of HIV-1 among IDUs may foster the emergence of highly homogeneous strains, including novel recombinants in regions with multiple subtypes.

scholarly journals Effect of Amino Acid Substitution of the V3 and Bridging Sheet Residues in Human Immunodeficiency Virus Type 1 Subtype C gp120 on CCR5 Utilization

2003 ◽  
Vol 77 (6) ◽  
pp. 3832-3837 ◽  
Author(s):  
Pirada Suphaphiphat ◽  
Arunee Thitithanyanont ◽  
Saowakon Paca-Uccaralertkun ◽  
Max Essex ◽  
Tun-Hou Lee
Keyword(s):  
Human Immunodeficiency Virus ◽  
Cell Fusion ◽  
Human Immunodeficiency Virus Type ◽  
Virus Type ◽  
Critical Role ◽  
Subtype C ◽  
Subtype B ◽  
Immunodeficiency Virus ◽  
Hiv 1

ABSTRACT The V3 loop and the bridging sheet domain of human immunodeficiency virus type 1 (HIV-1) subtype B envelope glycoprotein gp120 have been implicated in CCR5 coreceptor utilization. In this study, mutant envelope glycoproteins of a subtype C isolate containing substitutions in the V3 or C4 region were generated to determine which are required for efficient CCR5-dependent cell fusion and viral entry. We found that the V3 crown and C4 residues are relatively dispensable for cell-cell fusion, although some residues may be involved in the regulation of early postentry steps in viral replication. In contrast, seven highly conserved residues located in the V3 stem are critical for CCR5 utilization, which can explain the apparent paradox that the functional convergence in CCR5 usage by genetically divergent HIV-1 strains involves a variable region. The finding that C4 residues do not have a critical role may appear to contradict the current model that bridging sheet residues are involved in the gp120-CCR5 interaction. However, a plausible interpretation is that these C4 residues may have a distinct role in the binding and fusion steps of the gp120-CCR5 interaction.

scholarly journals Molecular Cloning and Phylogenetic Analysis of Human Immunodeficiency Virus Type 1 Subtype C: a Set of 23 Full-Length Clones from Botswana

1999 ◽  
Vol 73 (5) ◽  
pp. 4427-4432 ◽  
Author(s):  
Vladimir A. Novitsky ◽  
Monty A. Montano ◽  
Mary F. McLane ◽  
Boris Renjifo ◽  
Fredrik Vannberg ◽  
...  
Keyword(s):  
Human Immunodeficiency Virus ◽  
Human Immunodeficiency Virus Type ◽  
Virus Type ◽  
Southern Africa ◽  
Full Length ◽  
Subtype C ◽  
Subtype B ◽  
Immunodeficiency Virus ◽  
Hiv 1

ABSTRACT To better understand the virological aspect of the expanding AIDS epidemic in southern Africa, a set of 23 near-full-length clones of human immunodeficiency virus type 1 (HIV-1) representing eight AIDS patients from Botswana were sequenced and analyzed phylogenetically. All study viruses from Botswana belonged to HIV-1 subtype C. The interpatient diversity of the clones from Botswana was higher than among full-length isolates of subtype B or among a set of full-length HIV-1 genomes of subtype C from India (mean value of 9.1% versus 6.5 and 4.3%, respectively; P < 0.0001 for both comparisons). Similar results were observed in all genes across the entire viral genome. We suggest that the high level of HIV-1 diversity might be a typical feature of the subtype C epidemic in southern Africa. The reason or reasons for this diversity are unclear, but may include an altered replication efficiency of HIV-1 subtype C and/or the multiple introduction of different subtype C viruses.

scholarly journals Full-Length Human Immunodeficiency Virus Type 1 Genomes from Subtype C-Infected Seroconverters in India, with Evidence of Intersubtype Recombination

1999 ◽  
Vol 73 (1) ◽  
pp. 152-160 ◽  
Author(s):  
Kavita S. Lole ◽  
Robert C. Bollinger ◽  
Ramesh S. Paranjape ◽  
Deepak Gadkari ◽  
Smita S. Kulkarni ◽  
...  
Keyword(s):  
Human Immunodeficiency Virus ◽  
Human Immunodeficiency Virus Type ◽  
Virus Type ◽  
Full Length ◽  
Subtype C ◽  
Ctl Epitopes ◽  
Subtype B ◽  
Immunodeficiency Virus ◽  
Hiv 1

ABSTRACT The development of an effective human immunodeficiency virus type 1 (HIV-1) vaccine is likely to depend on knowledge of circulating variants of genes other than the commonly sequenced gag andenv genes. In addition, full-genome data are particularly limited for HIV-1 subtype C, currently the most commonly transmitted subtype in India and worldwide. Likewise, little is known about sequence variation of HIV-1 in India, the country facing the largest burden of HIV worldwide. Therefore, the objective of this study was to clone and characterize the complete genome of HIV-1 from seroconverters infected with subtype C variants in India. Cocultured HIV-1 isolates were obtained from six seroincident individuals from Pune, India, and virtually full-length HIV-1 genomes were amplified, cloned, and sequenced from each. Sequence analysis revealed that five of the six genomes were of subtype C, while one was a mosaic of subtypes A and C, with multiple breakpoints in env,nef, and the 3′ long terminal repeat as determined by both maximal χ2 analysis and phylogenetic bootstrapping. Sequences were compared for preservation of known cytotoxic T lymphocyte (CTL) epitopes. Compared with those of the HIV-1LAI sequence, 38% of well-defined CTL epitopes were identical. The proportion of nonconservative substitutions for Env, at 61%, was higher (P < 0.001) than those for Gag (24%), Pol (18%), and Nef (32%). Therefore, characterized CTL epitopes demonstrated substantial differences from subtype B laboratory strains, which were most pronounced in Env. Because these clones were obtained from Indian seroconverters, they are likely to facilitate vaccine-related efforts in India by providing potential antigens for vaccine candidates as well as for assays of vaccine responsiveness.

scholarly journals Genetic and Neutralization Properties of Subtype C Human Immunodeficiency Virus Type 1 Molecular env Clones from Acute and Early Heterosexually Acquired Infections in Southern Africa

2006 ◽  
Vol 80 (23) ◽  
pp. 11776-11790 ◽  
Author(s):  
Ming Li ◽  
Jesus F. Salazar-Gonzalez ◽  
Cynthia A. Derdeyn ◽  
Lynn Morris ◽  
Carolyn Williamson ◽  
...  
Keyword(s):  
Human Immunodeficiency Virus ◽  
Human Immunodeficiency Virus Type ◽  
Virus Type ◽  
Neutralizing Antibody ◽  
Luciferase Reporter ◽  
Subtype C ◽  
Subtype B ◽  
Immunodeficiency Virus ◽  
Hiv 1

ABSTRACT A standard panel of subtype C human immunodeficiency virus type 1 (HIV-1) Env-pseudotyped viruses was created by cloning, sequencing, and characterizing functional gp160 genes from 18 acute and early heterosexually acquired infections in South Africa and Zambia. In general, the gp120 region of these clones was shorter (most evident in V1 and V4) and less glycosylated compared to newly transmitted subtype B viruses, and it was underglycosylated but no different in length compared to chronic subtype C viruses. The gp120s also exhibited low amino acid sequence variability (12%) in V3 and high variability (39%) immediately downstream of V3, a feature shared with newly transmitted subtype B viruses and chronic viruses of both subtypes. When tested as Env-pseudotyped viruses in a luciferase reporter gene assay, all clones possessed an R5 phenotype and resembled primary isolates in their sensitivity to neutralization by HIV-1-positive plasmas. Results obtained with a multisubtype plasma panel suggested partial subtype preference in the neutralizing antibody response to infection. The clones were typical of subtype C in that all were resistant to 2G12 (associated with loss of N-glycosylation at position 295) and most were resistant to 2F5, but all were sensitive to 4E10 and many were sensitive to immunoglobulin G1b12. Finally, conserved neutralization epitopes in the CD4-induced coreceptor binding domain of gp120 were poorly accessible and were difficult to induce and stabilize with soluble CD4 on Env-pseudotyped viruses. These results illustrate key genetic and antigenic properties of subtype C HIV-1 that might impact the design and testing of candidate vaccines. A subset of these gp160 clones are suitable for use as reference reagents to facilitate standardized assessments of vaccine-elicited neutralizing antibody responses.

scholarly journals Phenotypic and Genotypic Comparisons of CCR5- and CXCR4-Tropic Human Immunodeficiency Virus Type 1 Biological Clones Isolated from Subtype C-Infected Individuals

2004 ◽  
Vol 78 (6) ◽  
pp. 2841-2852 ◽  
Author(s):  
Georgios Pollakis ◽  
Almaz Abebe ◽  
Aletta Kliphuis ◽  
Moustapha I. M. Chalaby ◽  
Margreet Bakker ◽  
...  
Keyword(s):  
Human Immunodeficiency Virus ◽  
Human Immunodeficiency Virus Type ◽  
Virus Type ◽  
Envelope Gene ◽  
Subtype C ◽  
Subtype B ◽  
Immature Dendritic Cells ◽  
Immunodeficiency Virus ◽  
Hiv 1

ABSTRACT Individuals infected with human immunodeficiency virus type 1 (HIV-1) subtype C infrequently harbour X4 viruses. We studied R5 and X4 biological clones generated from HIV-1 subtype C-infected individuals. All subtype C R5 viruses demonstrated slower profiles of replication on CD4+ lymphocytes in comparison to subtype B viruses, whereas subtype C X4 viruses replicated with comparable efficiency to subtype B X4 viruses. No differences were identified in CC or CXC chemokine inhibitions (RANTES and SDF-1α, respectively) between subtype C and subtype B viruses. Immature dendritic cells were shown in coculture experiments to similarly enhance the infection of subtype C and subtype B R5 as well as X4 viruses. By amino acid sequence analysis, we showed that the R5 and X4 subtype C gp120 envelope gene alterations were similar to those for a switching subtype B virus, specifically with respect to the V3 charge and envelope N-linked glycosylation patterns. By phylogenetic analysis, we showed that one patient was infected with HIV-1 C′ and the other was infected with HIV-1 C" and that one of the patients harbored a virus that was a recombinant in the gp120 env gene between an R5 and an X4 virus, with the resultant virus being R5. No differences were identified between the long terminal repeat regions of the subtype C R5 and X4 biological clones. These results indicate that even though R5 subtype C viruses are restrictive for virus replication, the R5-to-X4 phenotype switch can occur and does so in a manner similar to that of subtype B viruses.

scholarly journals A Reliable Phenotype Predictor for Human Immunodeficiency Virus Type 1 Subtype C Based on Envelope V3 Sequences

2006 ◽  
Vol 80 (10) ◽  
pp. 4698-4704 ◽  
Author(s):  
Mark A. Jensen ◽  
Mia Coetzer ◽  
Angélique B. van 't Wout ◽  
Lynn Morris ◽  
James I. Mullins
Keyword(s):  
Human Immunodeficiency Virus ◽  
Human Immunodeficiency Virus Type ◽  
Virus Type ◽  
Coreceptor Usage ◽  
Subtype C ◽  
Subtype B ◽  
Combining Data ◽  
Immunodeficiency Virus ◽  
Hiv 1

ABSTRACT In human immunodeficiency virus type 1 (HIV-1) subtype B infections, the emergence of viruses able to use CXCR4 as a coreceptor is well documented and associated with accelerated CD4 decline and disease progression. However, in HIV-1 subtype C infections, responsible for more than 50% of global infections, CXCR4 usage is less common, even in individuals with advanced disease. A reliable phenotype prediction method based on genetic sequence analysis could provide a rapid and less expensive approach to identify possible CXCR4 variants and thus increase our understanding of subtype C coreceptor usage. For subtype B V3 loop sequences, genotypic predictors have been developed based on position-specific scoring matrices (PSSM). In this study, we apply this methodology to a training set of 279 subtype C sequences of known phenotypes (228 non-syncytium-inducing [NSI] CCR5+ and 51 SI CXCR4+ sequences) to derive a C-PSSM predictor. Specificity and sensitivity distributions were estimated by combining data set bootstrapping with leave-one-out cross-validation, with random sampling of single sequences from individuals on each bootstrap iteration. The C-PSSM had an estimated specificity of 94% (confidence interval [CI], 92% to 96%) and a sensitivity of 75% (CI, 68% to 82%), which is significantly more sensitive than predictions based on other methods, including a commonly used method based on the presence of positively charged residues (sensitivity, 47.8%). A specificity of 83% and a sensitivity of 83% were achieved with a validation set of 24 SI and 47 NSI unique subtype C sequences. The C-PSSM performs as well on subtype C V3 loops as existing subtype B-specific methods do on subtype B V3 loops. We present bioinformatic evidence that particular sites may influence coreceptor usage differently, depending on the subtype.

scholarly journals Development of an Allele-Specific PCR for Detection of the K65R Resistance Mutation in Patients Infected with Subtype C Human Immunodeficiency Virus Type 1

2009 ◽  
Vol 54 (2) ◽  
pp. 907-911 ◽  
Author(s):  
Thomas A. Toni ◽  
Bluma G. Brenner ◽  
Eugene L. Asahchop ◽  
Michel Ntemgwa ◽  
Daniella Moisi ◽  
...  
Keyword(s):  
Human Immunodeficiency Virus ◽  
Human Immunodeficiency Virus Type ◽  
Virus Type ◽  
Subtype C ◽  
Subtype B ◽  
Immunodeficiency Virus ◽  
Minority Species ◽  
Allele Specific ◽  
Hiv 1

ABSTRACTThe selection of drug-resistant variants of human immunodeficiency virus type 1 (HIV-1) is an impediment to the efficiency of antiretroviral (ARV) therapy. We have developed an allele-specific real-time PCR assay to explore the presence of K65R minority species among treated HIV-1 subtype B and C infections. Thirty HIV-1 subtype C- and 26 subtype B-infected patients lacking K65R as determined by conventional sequencing methods were studied, and viral minority species were found in four HIV-1 subtype C samples.

scholarly journals Comparing the Ex Vivo Fitness of CCR5-Tropic Human Immunodeficiency Virus Type 1 Isolates of Subtypes B and C

2003 ◽  
Vol 77 (2) ◽  
pp. 1021-1038 ◽  
Author(s):  
Sarah C. Ball ◽  
Awet Abraha ◽  
Kalonji R. Collins ◽  
Andre J. Marozsan ◽  
Heather Baird ◽  
...  
Keyword(s):  
Human Immunodeficiency Virus ◽  
Human Immunodeficiency Virus Type ◽  
Virus Type ◽  
Relative Fitness ◽  
Subtype C ◽  
Unequal Distribution ◽  
Subtype B ◽  
Immunodeficiency Virus ◽  
Hiv 1

ABSTRACT Continual human immunodeficiency virus type 1 (HIV-1) evolution and expansion within the human population have led to unequal distribution of HIV-1 group M subtypes. In particular, recent outgrowth of subtype C in southern Africa, India, and China has fueled speculation that subtype C isolates may be more fit in vivo. In this study, nine subtype B and six subtype C HIV-1 isolates were added to peripheral blood mononuclear cell cultures for a complete pairwise competition experiment. All subtype C HIV-1 isolates were less fit than subtype B isolates (P < 0.0001), but intrasubtype variations in HIV-1 fitness were not significant. Increased fitness of subtype B over subtype C was also observed in primary CD4+ T cells and macrophages from different human donors but not in skin-derived human Langerhans cells. Detailed analysis of the retroviral life cycle during several B and C virus competitions indicated that the efficiency of host cell entry may have a significant impact on relative fitness. Furthermore, phyletic analyses of fitness differences suggested that, for a recombined subtype B/C HIV-1 isolate, higher fitness mapped to the subtype B env gene rather than the subtype C gag and pol genes. These results suggest that subtype B and C HIV-1 may be transmitted with equal efficiency (Langerhans cell data) but that subtype C isolates may be less fit following initial infection (T-cell and macrophage data) and may lead to slower disease progression.

scholarly journals Intra- and Intersubtype Alternative Pak2-Activating Structural Motifs of Human Immunodeficiency Virus Type 1 Nef

2006 ◽  
Vol 80 (17) ◽  
pp. 8824-8829 ◽  
Author(s):  
Eduardo O'Neill ◽  
Laura L. Baugh ◽  
Vladimir A. Novitsky ◽  
Myron E. Essex ◽  
J. Victor Garcia
Keyword(s):  
Human Immunodeficiency Virus ◽  
Human Immunodeficiency Virus Type ◽  
Virus Type ◽  
Subtype C ◽  
Structural Motifs ◽  
Subtype B ◽  
Immunodeficiency Virus ◽  
Future Drug ◽  
Hiv 1

ABSTRACT The design of antiviral strategies against human immunodeficiency virus type 1 (HIV-1) has been largely derived from studies of subtype B viruses, although they constitute only 12% of infections worldwide. At 50% of all HIV-1 infections worldwide, subtype C viruses are the most predominant. Here, we present evidence that subtype C Nefs display functional Pak2-activating motifs that differ from those found in subtype B and E Nefs. The identification of multiple Pak2-activating structural motifs that singly affect one Nef activity revealed a functional plasticity that has implications for future drug and vaccine design aimed at HIV-1 Nef and its effects on the deregulation of the immune system.

Sign in / Sign up

Export Citation Format

Share Document