HIV Type 1 Group M Clades Infecting Subjects From Rural Villages in Equatorial Rain Forests of Cameroon

Zhong, Ping; Burda, Sherri; Urbanski, Mateusz M.; Kenfack, Henriette; Tongo, Marcel; Heyndrickx, Leo; Nanfack, Aubin; Shang, Judith; Agyingi, Lucy; Zolla‐Pazner, Susan; Zekeng, Léopold; Nyambi, Phillipe N.

doi:10.1097/00126334-200212150-00007

Cited by 45 publications

(35 citation statements)

References 33 publications

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“…Cameroon is a country in West Central Africa that harbors a broad HIV-1 genetic diversity, including all HIV-1 groups (M, N, and O), all group M (sub-) subtypes, many CRFs, and a wide variety of ISRs, as reported previously Zhong et al, 2002Zhong et al, , 2003aBurda et al, 2004; and others [Nkengasong et al, 1994;Fonjungo et al, 2000;Heyndrickx et al, 2000;Morison et al, 2001]. Initial analysis of HIV-1 subtypes in the urban and semi-urban regions of Cameroon in the mid-1990s revealed the presence of diverse subtypes at different frequencies with subtype A accounting for 60%-65% of the infections [Nkengasong et al, 1994;Heyndrickx et al, 2000].…”

Section: Introductionmentioning

confidence: 64%

“…Our most recent molecular epidemiological studies in Cameroon in the years 2000-2003 show a continued predominance of CRF02_AG but also reveal the abundance of other recombinant strains. For example, sequence analysis of the pro gene of isolates obtained in the rural areas of Cameroon revealed that 60% were CRF02_AG , and additional analysis of several of these isolates in the gag and env genes showed that two-thirds were recombinants, of which almost half were CRF02_AG variants [Zhong et al, 2002[Zhong et al, , 2003a. Recombination between the predominant CRF02_AG and other HIV-1 subtypes in Cameroon eventually resulted in several CRF02_AG-containing ISRs [Zhong et al, 2002[Zhong et al, , 2003a including CRF09_cpx, which was identified recently in the town of Bamenda [Burda et al, 2004].…”

Section: Introductionmentioning

confidence: 99%

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Human immunodeficiency virus type 1 (HIV-1) circulating recombinant form 02_AG (CRF02_AG) has a higher in vitro replicative capacity than its parental subtypes A and G

et al. 2006

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Human immunodeficiency virus type 1 (HIV-1) circulating recombinant form (CRF) 02_AG is the predominant subtype in Cameroon, even more prevalent than the parental subtypes A and G. An important question that needs to be addressed is whether recombination in HIV-1 infection can lead to the emergence of viruses with biological advantages. The replicative capacity was investigated in peripheral blood mononuclear cells (PBMCs) of 13 R5-tropic primary HIV-1 isolates, including 5 CRF02_AG, 4 subtype A, and 4 subtype G viruses. HIV-1 subtype identity was defined by phylogeny either of the full-length genome or analysis of a combination of segments of the gag, pro, pol, and env genes followed by recombination breakpoint analysis. All viruses were grown on PBMCs for 11 days and culture supernatant was analyzed for reverse transcriptase (RT) activity and p24 production. On day 11 post-infection, CRF02_AG strains had a 1.4-1.9 times higher RT activity and reached a significantly higher level of p24 production than the parental subtypes A and G. Furthermore, the replication rate as measured by p24 production was 1.4 times higher for CRF02_AG strains compared to the subtypes A and G. This study suggests that the recombination event that led to CRF02_AG resulted in a variant with a better replicative capacity than its progenitors. This adaptation could contribute to the broader spread of HIV-1 CRF02_AG leading to its predominance in West Central Africa compared to the lower prevalence of its parental subtypes A and G.

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Section: Introductionmentioning

confidence: 64%

Section: Introductionmentioning

confidence: 99%

Human immunodeficiency virus type 1 (HIV-1) circulating recombinant form 02_AG (CRF02_AG) has a higher in vitro replicative capacity than its parental subtypes A and G

et al. 2006

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“…RNA extraction was performed on 100 l of plasma as described by Boom et al (4), followed by a single-tube reverse transcriptase (RT)-PCR (Access RT-PCR system, Promega, Madison, WI) to amplify the C2V5 region of env (40). The amplified products were sequenced and phylogenetically analyzed with reference subtype sequences to determine the virus subtypes as previously described (10,41).…”

Section: Methodsmentioning

confidence: 99%

Cross-Clade Neutralizing Activity of Human Anti-V3 Monoclonal Antibodies Derived from the Cells of Individuals Infected with Non-B Clades of Human Immunodeficiency Virus Type 1

Gorny¹,

Williams²,

Volsky³

et al. 2006

J Virol

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104

108

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During the past two decades, several epitopes that induce neutralizing antibodies (Abs) have been identified in the human immunodeficiency virus (HIV) envelope through studies of polyclonal and monoclonal Abs (MAbs). These epitopes include the V3 region defined with polyclonal Abs (30, 33) and several MAbs, such as 447-52D (16); the membrane-proximal external region in gp41 defined by MAbs 2F5 and 4E10 (6); the CD4-binding site on gp120 defined by MAb immunoglobulin G1b12 (IgG1b12) (7); and a glycan-rich region on gp120 defined by MAb 2G12 (37). With the exception of V3, none of these epitopes induce neutralizing Abs in the majority of infected humans. Thus, Abs to the membrane-proximal external region of gp41 (G. Shaw, H. Li, J. Decker, S. Allen, E. Hunter, E. Delaporte, M. Peters, B. Hahn, and F. Bibollet-Ruche, Abstr. AIDS Vaccine 2005, abstr. 29, 2005 (45), the CD4 binding site defined by IgG1b12 (25), and the designated carbohydrate moieties on gp120 (23, 37) are rare or absent from the sera of most HIV-infected individuals, and the epitope recognized by 2F5 (9,11,29) and the peptide mimotope for IgG1b12 (44) have failed to induce neutralizing Abs when used as experimental immunogens. Moreover, the recently described auto-reactive character of MAbs 2F5, 4E10, and IgG1b12, which recognize cardiolipin and/or double-stranded DNA, indicates that these epitopes may be problematic for the design of an anti-HIV vaccine (22). In contrast, the immunogenicity of the V3 region is reflected by the presence of anti-V3 Abs in the sera of essentially all HIV-infected individuals (38).Opinions about the V3 loop as an antigen for the induction of neutralizing Abs have changed over time. Early optimism related to the ability of anti-V3 MAbs to neutralize T-cell-lineadapted viruses was replaced by skepticism when it was suggested that the V3 of primary isolate JR-FL was "cryptic" (5). More recent data suggest that V3 is accessible on the surfaces of most virions (31) and that anti-V3 MAbs, such as 447-52D, can neutralize 62 to 92% of primary isolates that carry the epitope for which V3 is specific (3, 43). Nonetheless, recent studies have shown that V3 is masked in many viruses by the V1/V2 region (32) and/or by carbohydrate moieties on the envelope (39), both of which may contribute to the resistance of primary isolates (26,28). Moreover, it has been demonstrated in several studies that, despite the sequence variation in the V3 loop, many human anti-V3 Abs are cross-reactive (3,

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“…Human MAb 2182 was derived from a clade A virus-infected immigrant from China who is currently living in New York City (15), and MAbs 2557 and 2558 were produced from individuals who were infected with the CRF02AG virus subtype and are living in Cameroon. The clade A and CRF02AG env genes were identified by using a heteroduplex mobility assay and by sequencing, respectively (56). The irrelevant human MAb 1418 against parvovirus B19 was used as a negative control (10).…”

Section: Methodsmentioning

confidence: 99%

The V3 Loop Is Accessible on the Surface of Most Human Immunodeficiency Virus Type 1 Primary Isolates and Serves as a Neutralization Epitope

Górny¹,

Revesz

Williams³

et al. 2004

J Virol

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107

111

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Antibodies (Abs) against the V3 loop of the human immunodeficiency virus type 1 gp120 envelope glycoprotein were initially considered to mediate only type-specific neutralization of T-cell-line-adapted viruses. However, recent data show that cross-neutralizing V3 Abs also exist, and primary isolates can be efficiently neutralized with anti-V3 monoclonal Abs (MAbs). The neutralizing activities of anti-V3 polyclonal Abs and MAbs may, however, be limited due to antigenic variations of the V3 region, a lack of V3 exposure on the surface of intact virions, or Ab specificity. For clarification of this issue, a panel of 32 human anti-V3 MAbs were screened for neutralization of an SF162-pseudotyped virus in a luciferase assay. MAbs selected with a V3 fusion protein whose V3 region mimics the conformation of the native virus were significantly more potent than MAbs selected with V3 peptides. Seven MAbs were further tested for neutralizing activity against 13 clade B viruses in a single-round peripheral blood mononuclear cell assay. While there was a spectrum of virus sensitivities to the anti-V3 MAbs observed, 12 of the 13 viruses were neutralized by one or more of the anti-V3 MAbs. MAb binding to intact virions correlated significantly with binding to solubilized gp120s and with the potency of neutralization. These results demonstrate that the V3 loop is accessible on the native virus envelope, that the strength of binding of anti-V3 Abs correlates with the potency of neutralization, that V3 epitopes may be shared rather than type specific, and that Abs against the V3 loop, particularly those targeting conformational epitopes, can mediate the neutralization of primary isolates.The third variable domain (V3) of the human immunodeficiency virus type 1 (HIV-1) gp120 envelope glycoprotein is critical for the formation of syncytia and for virus entry into target cells (24,55). These functions are mediated by the interaction of the V3 loop with chemokine receptors and are maintained despite the sequence variation that characterizes this region of the virus envelope (18, 51). Indeed, contrary to its name, the V3 loop is characterized by a constant size of 30 to 35 amino acids, a conserved type II ␤-turn at its tip, a disulfide bond at its base, and a net positive charge (26, 28). Conserved features are also suggested by the structure of the V3 loop discerned by nuclear magnetic resonance studies (47, 52), and conserved elements in the V3 crown and stem are mandatory features for coreceptor interactions (9, 50). All of these structural constraints appear to be imposed by the required interaction of the V3 loop with the coreceptors for HIV-1, CXCR4 or CCR5, and suggest that this region of the virus envelope should induce antibodies (Abs) that are crossreactive among isolates and inhibitory to virus infectivity.Initial studies of anti-V3 Abs, induced by brief immunization protocols in animals and tested against a limited number of T-cell-line-adapted (TCLA) strains of the virus, suggested, however, that anti-V3 Abs were type spec...

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HIV Type 1 Group M Clades Infecting Subjects From Rural Villages in Equatorial Rain Forests of Cameroon

Cited by 45 publications

References 33 publications

Human immunodeficiency virus type 1 (HIV-1) circulating recombinant form 02_AG (CRF02_AG) has a higher in vitro replicative capacity than its parental subtypes A and G

Human immunodeficiency virus type 1 (HIV-1) circulating recombinant form 02_AG (CRF02_AG) has a higher in vitro replicative capacity than its parental subtypes A and G

Cross-Clade Neutralizing Activity of Human Anti-V3 Monoclonal Antibodies Derived from the Cells of Individuals Infected with Non-B Clades of Human Immunodeficiency Virus Type 1

The V3 Loop Is Accessible on the Surface of Most Human Immunodeficiency Virus Type 1 Primary Isolates and Serves as a Neutralization Epitope

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