South African HIV-1 Subtype Research Articles

Cantilever-centric mechanism of cooperative non-active site mutations in HIV protease: Implications for flap dynamics

The HIV-1 protease is an important drug target in antiretroviral therapy due to the crucial role it plays in viral maturation. A greater understanding of the dynamics of the protease as a result of drug-induced mutations has been successfully elucidated using computational models in the past. We performed induced-fit docking studies and molecular dynamics simulations on the wild-type South African HIV-1 subtype C protease and two non-active site mutation-containing protease variants; HP3 PR and HP4 PR. The HP3 PR contained the I13V, I62V, and V77I mutations while HP4 PR contained the same mutations with the addition of the L33F mutation. The simulations were initiated in a cubic cell universe containing explicit solvent, with the protease variants beginning in the fully closed conformation. The trajectory for each simulation totalled 50 ns. The results indicate that the mutations increase the dynamics of the flap, hinge, fulcrum and cantilever regions when compared to the wild-type protease while in complex with protease inhibitors. Specifically, these mutations result in the protease favouring the semi-open conformation when in complex with inhibitors. Moreover, the HP4 PR adopted curled flap tip conformers which coordinated several water molecules into the active site in a manner that may reduce inhibitor binding affinity. The mutations affected the thermodynamic landscape of inhibitor binding as there were fewer observable chemical contacts between the mutated variants and saquinavir, atazanavir and darunavir. These data help to elucidate the biophysical basis for the selection of cooperative non-active site mutations by the HI virus.

Acquired HIV-1 Protease Conformational Flexibility Associated with Lopinavir Failure May Shape the Outcome of Darunavir Therapy after Antiretroviral Therapy Switch.

Understanding the underlying molecular interaction during a therapy switch from lopinavir (LPV) to darunavir (DRV) is essential to achieve long-term virological suppression. We investigated the kinetic and structural characteristics of multidrug-resistant South African HIV-1 subtype C protease (HIV-1 PR) during therapy switch from LPV to DRV using enzyme activity and inhibition assay, fluorescence spectroscopy, and molecular dynamic simulation. The HIV-1 protease variants were from clinical isolates with a combination of drug resistance mutations; MUT-1 (M46I, I54V, V82A, and L10F), MUT-2 (M46I, I54V, L76V, V82A, L10F, and L33F), and MUT-3 (M46I, I54V, L76V, V82A, L90M, and F53L). Enzyme kinetics analysis shows an association between increased relative resistance to LPV and DRV with the progressive decrease in the mutant HIV-1 PR variants’ catalytic efficiency. A direct relationship between high-level resistance to LPV and intermediate resistance to DRV with intrinsic changes in the three-dimensional structure of the mutant HIV-1 PR as a function of the multidrug-resistance mutation was observed. In silico analysis attributed these structural adjustments to the multidrug-resistance mutations affecting the LPV and DRV binding landscape. Though DRV showed superiority to LPV, as a lower concentration was needed to inhibit the HIV-1 PR variants, the inherent structural changes resulting from mutations selected during LPV therapy may dynamically shape the DRV treatment outcome after the therapy switch.

Kinetic and thermodynamic characterisation of HIV-protease inhibitors against E35D↑G↑S mutant in the South African HIV-1 subtype C protease

Herein, we report the effect of nine FDA approved protease inhibitor drugs against a new HIV-1 subtype C mutant protease, E35D↑G↑S. The mutant has five mutations, E35D, two insertions, position 36 (G and S), and D60E. Kinetics, inhibition constants, vitality, Gibbs free binding energies are reported. The variant showed a decreased affinity for substrate and low catalytic efficiency compared to the wild type. There was a significant decrease in the binding of seven FDA approved protease inhibitors against the mutant (p < .0001). Amprenavir and ritonavir showed the least decrease, but still significant reduced activity in comparison to the wildtype (4 and 5 folds, respectively, p = .0021 and .003, respectively). Nelfinavir and atazanavir were the worst inhibitors against the variant as seen from the IC50, with values of 1401 ± 3.0 and 685 ± 3.0 nM, respectively. Thermodynamics data showed less favourable Gibbs free binding energies for the protease inhibitors to the mutant.

Exploring the flap dynamics of the South African HIV subtype C protease in presence of FDA-approved inhibitors: MD study.

HIV-1 protease (HIV PR) is considered as one of the most attractive targets for the treatment of HIV and the impact of flap dynamics of HIV PR on the binding affinities of protease inhibitors (PIs) is a crucial ongoing research field. Recently, our research group evaluated the binding affinities of different FDA approved PIs against the South African HIV-1 subtype C (C-SA) protease (PR). The CSA-HIV PR displayed weaker binding affinity for most of the clinical PIs compared to HIV-1 B subtype for West and Central Europe, the Americas. In the current work, the flap dynamics of four different systems of HIV-1 C-SA PR complexed to FDA approved second generation PIs and its impact on binding was explored over the molecular dynamic trajectories. It was observed that the interactions of the selected drugs with the binding site residues of the protease may not be the major contributor for affinity towards PIs. Various post-MD analyses were performed, also entropic contributions, solvation free energies and hydrophobic core formation interactions were studied to assess how the flap dynamics of C-SA PR which is affected by such factors. From these contributions, large van der Waals interactions and low solvation free energies were found to be major factors for the higher activity of ATV against C-SA HIV PR. Furthermore, a comparatively stable hydrophobic core may be responsible for higher stability of the PR flaps of the ATV complex. The outcome of this study provides significant guidance to how the flap dynamics of C-SA PR is affected by various factors as a result of the binding affinity of various protease inhibitors. It will also assist with the design of potent inhibitors against C-SA HIV PR that apart from binding in the active site of PR can interacts with the flaps to prevent opening of the flaps resulting in inactivation of the protease.

Drug susceptibility and replication capacity of a rare HIV-1 subtype C protease hinge region variant.

Protease inhibitors form the main component of second-line antiretroviral treatment in South Africa. Despite their efficacy, mutations arising within the HIV-1 gag and protease coding regions contribute to the development of resistance against this class of drug. In this paper we investigate a South African HIV-1 subtype C Gag-protease that contains a hinge region mutation and insertion (N37T↑V). In vitro single-cycle drug susceptibility and viral replication capacity assays were performed on W1201i, a wild-type reference isolate (MJ4) and a chimeric construct (MJ4GagN37T↑VPR). Additionally, enzyme assays were performed on the N37T↑V protease and a wild-type reference protease. W1201i showed a small (threefold), but significant (P<0.0001) reduction in drug susceptibility to darunavir compared with MJ4. Substitution of W1201i-Gag with MJ4-Gag resulted in an additional small (twofold), but significant (P<0.01) reduction in susceptibility to lopinavir and atazanavir. The W1201i pseudovirus had a significantly (P<0.01) reduced replication capacity (16.4%) compared with the MJ4. However, this was dramatically increased to 164% (P<0.05) when W1201i-Gag was substituted with MJ4-Gag. Furthermore, the N37T↑V protease displayed reduced catalytic processing compared with the SK154 protease. Collectively, these data suggest that the N37T↑V mutation and insertion increases viral infectivity and decreases drug susceptibility. These variations are classified as secondary mutations, and indirectly impact inhibitor binding, enzyme fitness and enzyme stability. Additionally, polymorphisms arising in Gag can modify the impact of protease with regards to viral replication and susceptibility to protease inhibitors.

Molecular dynamics and ligand docking of a hinge region variant of South African HIV-1 subtype C protease

HIV-1 protease is an important antiretroviral drug target due to its key role in viral maturation. Computational models have been successfully used in the past to understand the dynamics of HIV-1 protease variants. We performed molecular dynamics simulations and induced fit docking on a wild-type South African HIV-1 subtype C protease and an N37T↑V hinge region variant. The simulations were initiated in a cubic cell universe and run in explicit solvent, with the wild-type and variant proteases in the fully closed conformation and under periodic boundary conditions. The trajectory for each simulation totalled 20 ns. The results indicate that the N37T↑V hinge region mutation and insertion alter the molecular dynamics of the flap and hinge regions when compared to the wild-type protease. Specifically, the destabilisation of the hinge region allowed a larger and protracted opening of the flap region due to the formation of two key hinge/cantilever salt-bridges, which are absent in the wild-type protease. Domain-domain anti-correlation was observed between the flap and hinge region for both models. However, the N37T↑V variant protease displayed a lower degree of anti-correlation. The mutations affected the thermodynamic landscape of inhibitor binding as there were fewer observable chemical contacts between the N37T↑V variant protease and lopinavir, atazanavir and darunavir, respectively. These data elucidate the biophysical basis for the selection of hinge region insertion mutations by the HI virus.

I36T↑T mutation in South African subtype C (C-SA) HIV-1 protease significantly alters protease-drug interactions.

The efficacy of HIV-1 protease (PR) inhibition therapies is often compromised by the emergence of mutations in the PR molecule that reduces the binding affinity of inhibitors while maintaining viable catalytic activity and affinity for natural substrates. In the present study, we used a recombinant HIV-1 C-SA PR and a recently reported variant for inhibition (Ki, IC50) and thermodynamic studies against nine clinically used inhibitors. This is the first time that binding free energies for C-SA PR and the mutant are reported. This variant PR harbours a mutation and insertion (I36T↑T) at position 36 of the C-SA HIV-1 PR, and did not show a significant difference in the catalytic effect of the HIV-1 PR. However, the nine clinically approved HIV PR drugs used in this study demonstrated weaker inhibition and lower binding affinities toward the variant when compared to the wild type HIV-1 PR. All the protease inhibitors (PIs), except Amprenavir and Ritonavir exhibited a significant decrease in binding affinity (p<0.0001). Darunavir and Nelfinavir exhibited the weakest binding affinity, 155- and 95-fold decreases respectively, toward the variant. Vitality values for the variant PR, against the seven selected PIs, confirm the impact of the mutation and insertion on the South African HIV-1 subtype C PR. This information has important clinical implications for thousands of patients in Sub-Saharan Africa.

Functional characterization of Vif proteins from HIV-1 infected patients with different APOBEC3G haplotypes.

The human cytidine deaminase APOBEC3G (A3G) potently restricts HIV-1 but the virus, in turn, expresses a Vif protein which degrades A3G. A natural A3G-H186R variant, common in African populations, has been associated with a more rapid AIDS disease progression, but the underlying mechanism remains unknown. We hypothesized that differences in HIV-1 Vif activity towards A3G wild type and A3G-H186R contribute to the distinct clinical AIDS manifestation. Vif variants were cloned from plasma samples of 26 South African HIV-1 subtype C infected patients, which either express wild type A3G or A3G-H186R. The Vif alleles were assessed for their ability to counteract A3G variants using western blot and single-cycle infectivity assays. We obtained a total of 392 Vif sequences which displayed an amino acid sequence difference of 6.2-19.2% between patients. The intrapatient Vif diversities from patient groups A3G, A3G and A3G were similar. Vif variants obtained from patients expressing A3G and A3G were capable of counteracting both A3G variants with similar efficiency. However, the antiviral activity of A3G-H186R was significantly reduced in both the presence and absence of Vif, indicating that the A3G-H186R variant intrinsically exerts less antiviral activity. A3G wild type and A3G-H186R are equally susceptible to counteraction by Vif, regardless of whether the Vif variant was obtained from A3G and A3G patients. However, the A3G-H186R variant intrinsically displayed lower antiviral activity, which could explain the higher plasma viral loads and accelerated disease progression reported for patients expressing A3G.

South African HIV-1 subtype C transmitted variants with a specific V2 motif show higher dependence on α4β7 for replication.

BackgroundThe integrin α4β7 mediates the trafficking of immune cells to the gut associated lymphoid tissue (GALT) and is an attachment factor for the HIV gp120 envelope glycoprotein. We developed a viral replication inhibition assay to more clearly evaluate the role of α4β7 in HIV infection and the contribution of viral and host factors.ResultsReplication of 60 HIV-1 subtype C viruses collected over time from 11 individuals in the CAPRISA cohort were partially inhibited by antibodies targeting α4β7. However, dependence on α4β7 for replication varied substantially among viral isolates from different individuals as well as over time in some individuals. Among 8 transmitted/founder (T/F) viruses, α4β7 reactivity was highest for viruses having P/SDI/V tri-peptide binding motifs. Mutation of T/F viruses that had LDI/L motifs to P/SDI/V resulted in greater α4β7 reactivity, whereas mutating P/SDI/V to LDI/L motifs was associated with reduced α4β7 binding. P/SDI/V motifs were more common among South African HIV subtype C viruses (35%) compared to subtype C viruses from other regions of Africa (<8%) and to other subtypes, due in part to a founder effect. In addition, individuals with bacterial vaginosis (BV) and who had higher concentrations of IL-7, IL-8 and IL-1α in the genital tract had T/F viruses with higher α4β7 dependence for replication, suggesting that viruses with P/SDI/V motifs may be preferentially transmitted in the presence of BV in this population.ConclusionsCollectively, these data suggest a role for α4β7 in HIV infection that is influenced by both viral and host factors including the sequence of the α4β7 binding motif, the cytokine milieu and BV in the genital tract. The higher frequency of P/SDI/V sequences among South African HIV-1 subtype C viruses may have particular significance for the role of α4β7 in this geographical region.Electronic supplementary materialThe online version of this article (doi:10.1186/s12977-015-0183-3) contains supplementary material, which is available to authorized users.

High prevalence of the K65R mutation in HIV-1 subtype C infected patients failing tenofovir-based first-line regimens in South Africa.

BackgroundTenofovir (TDF) has replaced stavudine (d4T) as the preferred nucleoside reverse transcriptase inhibitor (NRTI) in first-line regimens in South Africa, but limited information is available on the resistance patterns that develop after the introduction of TDF. This study investigated the antiretroviral drug resistance patterns in South African HIV-1 subtype C-infected patients failing stavudine- (d4T) and tenofovir- (TDF) based first-line regimens and assess the suitability of TDF as the preferred first-line nucleotide reverse transcriptase inhibitor (NRTI).MethodsResistance patterns of HIV-1 from 160 adult patients virologically failing TDF- (n = 80) and d4T- (n = 80) based first-line regimens were retrospectively analyzed. The pol gene was sequenced using an in-house protocol and mutations were analysed using the IAS-USA 2014 Drug Resistance Mutation list.ResultsCompared to d4T-exposed patients (n = 7), patients failing on a TDF-containing regimen (n = 43) were almost 5 times more likely to present with a K65R mutation (aRR 4.86 95% CI 2.29 – 10.34). Y115F was absent in the d4T group, and detected in 13.8% (n = 11) of TDF-exposed patients, p = 0.0007. Virus from 9 of the 11 patients (82.0%) who developed the Y115F mutation also developed K65R. Intermediate or high-level resistance to most NRTIs was common in the TDF-treatment group, but these patients twice more likely to remain susceptible to AZT as compared to those exposed to d4T (aRR 2.09 95% CI 1.13 – 3.90).ConclusionThe frequency of the TDF induced K65R mutation was higher in our setting compared to non-subtype C dominated countries. However, despite the higher frequency of cross-resistance to NRTIs, most patients remained susceptible to AZT, which is reflected in the South African treatment guidelines that recommend AZT as an essential component of second-line regimens.

Amide hydrogen exchange in HIV-1 subtype B and C proteases - insights into reduced drug susceptibility and dimer stability

Since its identification, HIV has continued to have a detrimental impact on the lives of millions of people throughout the world. The protease of HIV is a major target in antiviral treatment. The South African HIV-1 subtype C (C-SA) protease displays weaker binding affinity for some clinically approved protease inhibitors in comparison with the HIV-1 subtype B protease. The heavy HIV burden in sub-Saharan Africa, where subtype C HIV-1 predominates, makes this disparity a topic of great interest. In light of this, the enzyme activity and affinity of protease inhibitors for the subtype B and C-SA proteases were determined. The relative vitality, indicating the selective advantage of polymorphisms, of the C-SA protease relative to the subtype B protease in the presence of ritonavir and darunavir was four- and tenfold greater, respectively. Dynamic differences that contribute to the reduced drug susceptibility of the C-SA protease were investigated by performing hydrogen-deuterium exchange/mass spectrometry (HDX/MS) on unbound subtype B and C-SA proteases. The reduced propensity to form the E35-R57 salt bridge, and alterations in the hydrophobic core of the C-SA protease, are proposed to affect the anchoring of the flexible flaps, resulting in an increased proportion of the fully open flap conformation. HDX/MS data suggested that the N-terminus of both proteases is less stable than the C-terminus of the proteases, thus explaining the increased efficacy of dimerization inhibitors targeted toward the C-terminus of HIV proteases. As far as we are aware, this is the first report on assessment of HIV protease dynamics using HDX/MS.

F99 is Critical for Dimerization and Activation of South African HIV-1 Subtype C Protease

HIV-1 protease (PR) is an obligate homodimer which plays a pivotal role in the maturation and hence propagation of HIV. Although successful developments on PR active site inhibitors have been achieved, the major limiting factor has been the emergence of HIV drug-resistant strains. Disruption of the dimer interface serves as an alternative mechanism to inactivate the enzyme. The terminal residue, F99, was mutated to an alanine to investigate its contribution to dimer stability in the South African HIV-1 subtype C (C-SA) PR. The F99A PR and wild-type C-SA PR were overexpressed and purified. The activities of the PRs and their ability to bind an active site inhibitor, acetyl-pepstatin, were determined in vitro. The F99A PR showed no activity and the inability to bind to the inhibitor. Secondary and quaternary structure analysis were performed and revealed that the F99A PR is monomeric with reduced β-sheet content. The mutation of F99 to alanine disrupted the presumed 'lock-and-key' motif at the terminal dimer interface, in turn creating a cavity at the N- and C-terminal antiparallel β-sheet. These findings support the design of inhibitors targeting the C-terminus of the C-SA PR, centered on interactions with the bulky F99.

Structural insights into the South African HIV-1 subtype C protease: impact of hinge region dynamics and flap flexibility in drug resistance

The HIV protease plays a major role in the life cycle of the virus and has long been a target in antiviral therapy. Resistance of HIV protease to protease inhibitors (PIs) is problematic for the effective treatment of HIV infection. The South African HIV-1 subtype C protease (C-SA PR), which contains eight polymorphisms relative to the consensus HIV-1 subtype B protease, was expressed in Escherichia coli, purified, and crystallized. The crystal structure of the C-SA PR was resolved at 2.7 Å, which is the first crystal structure of a HIV-1 subtype C protease that predominates in Africa. Structural analyses of the C-SA PR in comparison to HIV-1 subtype B proteases indicated that polymorphisms at position 36 of the homodimeric HIV-1 protease may impact on the stability of the hinge region of the protease, and hence the dynamics of the flap region. Molecular dynamics simulations showed that the flap region of the C-SA PR displays a wider range of movements over time as compared to the subtype B proteases. Reduced stability in the hinge region resulting from the absent E35-R57 salt bridge in the C-SA PR, most likely contributes to the increased flexibility of the flaps which may be associated with reduced susceptibility to PIs.An animated interactive 3D complement (I3DC) is available in Proteopedia at http://proteopedia.org/w/Journal:JBSD:36

Comparison of the neutralization sensitivity of South African and Indian HIV-1 subtype C viruses to South African plasma antibodies

Methods Plasma from 44 chronically HIV-1 subtype C infected SA individuals in the CAPRISA 002 Acute Infection cohort were used to assess the neutralization sensitivity of 10 SA and 9 Indian Tier 2 viruses in a TZM-bl assay. Intra-subtype neutralization activity between SA and Indian viruses was determined. The envelope sequence of the Indian panel was analyzed in order to identify epitopes known to be targeted by the neutralizing antibodies in a subset of the CAPRISA plasmas.

Origin and Dynamics of HIV-1 Subtype C Infection in India

ObjectiveTo investigate the geographical origin and evolution dynamics of HIV-1 subtype C infection in India.DesignNinety HIV-1 subtype C env gp120 subtype C sequences from India were compared with 312 env gp120 reference subtype C sequences from 27 different countries obtained from Los Alamos HIV database. All the HIV-1 subtype C env gp120 sequences from India were used for the geographical origin analysis and 61 subtype C env gp120 sequences with known sampling year (from 1991 to 2008) were employed to determine the origin of HIV infection in India.MethodsPhylogenetic analysis of HIV-1 env sequences was used to investigate the geographical origin and tMRCA of Indian HIV-1 subtype C. Evolutionary parameters including origin date and demographic growth patterns of Indian subtype C were estimated using a Bayesian coalescent-based approach under relaxed molecular clock models.FindingsThe majority of the analyzed Indian and South African HIV-1 subtype C sequences formed a single monophyletic cluster. The most recent common ancestor date was calculated to be 1975.56 (95% HPD, 1968.78–1981.52). Reconstruction of the effective population size revealed three phases of epidemic growth: an initial slow growth, followed by exponential growth, and then a plateau phase approaching present time. Stabilization of the epidemic growth phase correlated with the foundation of National AIDS Control Organization in India.InterpretationIndian subtype C originated from a single South African lineage in the middle of 1970s. The current study emphasizes not only the utility of HIV-1 sequence data for epidemiological studies but more notably highlights the effectiveness of community or government intervention strategies in controlling the trend of the epidemic.

Case report of the rare deletion at codon 69 of reverse transcriptase in a South African HIV-1 subtype C infected patient

Case report of the rare deletion at codon 69 of reverse transcriptase in a South African HIV-1 subtype C infected patient

A prime–boost immunisation regimen using recombinant BCG and Pr55gag virus-like particle vaccines based on HIV type 1 subtype C successfully elicits Gag-specific responses in baboons

Mycobacterium bovis BCG is considered an attractive live bacterial vaccine vector. In this study, we investigated the immune response of baboons to a primary vaccination with recombinant BCG (rBCG) constructs expressing the gag gene from a South African HIV-1 subtype C isolate, and a boost with HIV-1 subtype C Pr55gag virus-like particles (Gag VLPs). Using an interferon enzyme-linked immunospot assay, we show that although these rBCG induced only a weak or an undetectable HIV-1 Gag-specific response on their own, they efficiently primed for a Gag VLP boost, which strengthened and broadened the immune responses. These responses were predominantly CD8+ T cell-mediated and recognised similar epitopes as those targeted by humans with early HIV-1 subtype C infection. In addition, a Gag-specific humoral response was elicited. These data support the development of HIV-1 vaccines based on rBCG and Pr55gag VLPs.

Molecular Characterization of the HIV Type 1 Subtype C Accessory Genesvif,vpr, andvpu

HIV-1 Vif, Vpr, and Vpu proteins have a profound effect on efficient viral replication and pathogenesis. This study describes the genotypic characterisation of vif , vpr and vpu from 20 South African HIV-1 subtype C primary isolates, and extensive analysis and comparison of known motifs. All HIV-1 subtype C Vif, Vpr and Vpu proteins revealed the presence of highly conserved structural and functional motifs similar to other sub-types, for example, the Vif-APOBEC3G interaction domains. However, several differences were noted when these sequences were compared to subtype B, such as the presence of the LRLL motif which has been implicated in targeting subtype C Vpu predominantly to the cell surface, instead of the Golgi apparatus. A better understanding of the structure/function relationship of these proteins may lead to the development of new classes of antiviral drugs. These results indicate that antiviral drugs that target the conserved functional domains within Vif, Vpr or Vpu could be active against all circulating subtypes, including HIV-1 subtype C.

HIV type 1 V3 region subtyping in KwaZulu-Natal, a high-seroprevalence South African region.

AIDS Research and Human RetrovirusesVol. 14, No. 11 Sequence Note: HIV Type 1 V3 Region Subtyping in KwaZulu-Natal, a High-Seroprevalence South African RegionDAYA MOODLEY, TRACEY-LEE SMITH, ESTRELITA J. VAN RENSBURG, JACK MOODLEY, and SUSAN ENGELBRECHTDAYA MOODLEYSearch for more papers by this author, TRACEY-LEE SMITHSearch for more papers by this author, ESTRELITA J. VAN RENSBURGSearch for more papers by this author, JACK MOODLEYSearch for more papers by this author, and SUSAN ENGELBRECHTSearch for more papers by this authorPublished Online:15 Mar 2009https://doi.org/10.1089/aid.1998.14.1015AboutSectionsPDF/EPUB Permissions & CitationsPermissionsDownload CitationsTrack CitationsAdd to favorites Back To Publication ShareShare onFacebookTwitterLinked InRedditEmail FiguresReferencesRelatedDetailsCited byThe Reverse Transcriptase 67N 70R 215Y Genotype Is the Predominant TAM Pathway Associated with Virologic Failure among HIV Type 1C-Infected Adults Treated with ZDV/ddI-Containing HAART in Southern Africa Vlad Novitsky, C. William Wester, Victor DeGruttola, Hermann Bussmann, Simani Gaseitsiwe, Ann Thomas, Sikhulile Moyo, Rosemary Musonda, Erik Van Widenfelt, Richard G. Marlink, and M. Essex3 August 2007 | AIDS Research and Human Retroviruses, Vol. 23, No. 7Genotypic and phenotypic analysis of theenv gene from South African HIV-1 subtype B and C isolates12 August 2002 | Journal of Medical Virology, Vol. 68, No. 2Rapid Characterization of HIV Clade C-Specific Cytotoxic T Lymphocyte Responses in Infected African Children and Adults25 January 2006 | Annals of the New York Academy of Sciences, Vol. 918, No. 1Differential Narrow Focusing of Immunodominant Human Immunodeficiency Virus Gag-Specific Cytotoxic T-Lymphocyte Responses in Infected African and Caucasoid Adults and ChildrenJournal of Virology, Vol. 74, No. 12HIV Type 1 V3 Domain Serotyping and Genotyping in Gauteng, Mpumalanga, KwaZulu-Natal, and Western Cape Provinces of South Africa S. Engelbrecht, T.-L. Smith, P. Kasper, E. Faatz, M. Zeier, D. Moodley, C.G. Clay, and E.J. Van Rensburg5 July 2004 | AIDS Research and Human Retroviruses, Vol. 15, No. 4A Predominantly HIV Type 1 Subtype C-Restricted Epidemic in South African Urban Populations J.H. Van Harmelen, E. Van Der Ryst, A.S. Loubser, D. York, S. Madurai, S. Lyons, R. Wood, and C. Williamson5 July 2004 | AIDS Research and Human Retroviruses, Vol. 15, No. 4 Volume 14Issue 11Jul 1998 To cite this article:DAYA MOODLEY, TRACEY-LEE SMITH, ESTRELITA J. VAN RENSBURG, JACK MOODLEY, and SUSAN ENGELBRECHT.Sequence Note: HIV Type 1 V3 Region Subtyping in KwaZulu-Natal, a High-Seroprevalence South African Region.AIDS Research and Human Retroviruses.Jul 1998.1015-1018.http://doi.org/10.1089/aid.1998.14.1015Published in Volume: 14 Issue 11: March 15, 2009PDF download

HIV type 1 coreceptors, neutralization serotypes, and vaccine development.

HIV type 1 coreceptors, neutralization serotypes, and vaccine development.