HIV-1 subtype C syncytium- and non-syncytium-inducing phenotypes and coreceptor usage among Ethiopian patients with AIDS

Abebe, Almaz; Demissie, Dereje Bayissa; Goudsmit, Jaap; Brouwer, Margreet; Kuiken, Carla; Pollakis, Georgios; Schuitemaker, Hanneke; Fontanet, Arnaud; Wit, Tobias F. Rinke de

doi:10.1097/00002030-199907300-00006

Cited by 150 publications

(94 citation statements)

References 32 publications

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“…Subtype C envelopes have low V3 charges and a high frequency of V3 glycosylation, which is in support of reports describing a low frequency of SI isolates among subtype C-infected individuals even when the patients had low CD4 ϩ cell counts and had progressed to AIDS (69). In accordance, HIV-1 subtypes D and E demonstrate the highest frequency of V3 de-glycosylation, even at the lower V3 charges, and both these subtypes reportedly have a high frequency of SI viruses among infected individuals (71,72).…”

Section: Figsupporting

confidence: 87%

N-Linked Glycosylation of the HIV Type-1 gp120 Envelope Glycoprotein as a Major Determinant of CCR5 and CXCR4 Coreceptor Utilization

Pollakis

Kang

Kliphuis

et al. 2001

Journal of Biological Chemistry

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The variable V1V2 and V3 regions of the human immunodeficiency virus type-1 (HIV-1) envelope glycoprotein (gp120) can influence viral coreceptor usage. To substantiate this we generated isogenic HIV-1 molecularly cloned viruses that were composed of the HxB2 envelope backbone containing the V1V2 and V3 regions from viruses isolated from a patient progressing to disease. We show that the V3 amino acid charge per se had little influence on altering the virus coreceptor phenotype. The V1V2 region and its N-linked glycosylation degree were shown to confer CXCR4 usage and provide the virus with rapid replication kinetics. Loss of an Nlinked glycosylation site within the V3 region had a major influence on the virus switching from the R5 to X4 phenotype in a V3 charge-dependent manner. The loss of this V3 N-linked glycosylation site was also linked with the broadening of the coreceptor repertoire to incorporate CCR3. By comparing the amino acid sequences of primary HIV-1 isolates, we identified a strong association between high V3 charge and the loss of this V3 N-linked glycosylation site. These results demonstrate that the N-linked glycosylation pattern of the HIV-1 envelope can strongly influence viral coreceptor utilization and the R5 to X4 switch.

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Section: Figsupporting

confidence: 87%

N-Linked Glycosylation of the HIV Type-1 gp120 Envelope Glycoprotein as a Major Determinant of CCR5 and CXCR4 Coreceptor Utilization

Pollakis

Kang

Kliphuis

et al. 2001

Journal of Biological Chemistry

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206

221

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“…quency of syncytium induction (1). Sequence variability in Env V3 among subtype C viruses is not associated with the presence of basic amino acid substitutions, and this is in contrast to that of subtype B viruses (4,9).…”

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confidence: 96%

Human Immunodeficiency Virus Type 1 Subtype C Exhibits Higher Transactivation Activity of Tat than Subtypes B and E

Kurosu

Mukai

Komoto

et al. 2002

Microbiology and Immunology

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Although human immunodeficiency virus type 1 (HIV‐1) subtypes C and E are expanding faster and seem to be of greater global significance than HIV‐1 subtype B, there is only little information about Tat activity of such non‐B subtypes. Here, we showed evidence that subtype C Tat exhibits higher transcriptional activity from the HIV‐1 long‐terminal repeat (LTR) in a human T‐cell line, compared with subtypes B and E. This higher activity of subtype C Tat was not due to the LTR, but to the Tat sequence variability. We examined three candidate regions with sequence for the higher activity of subtype C Tat, such as the cysteine‐rich motif, the basic domain, and the 2nd exon. The results showed that the variation in subtype C Tat at two amino acid residues, Ser57 and Glu63 in stead of Arg57 and Gln63 in subtypes B and E, within and close to the basic domain were involved in the higher activity of subtype C Tat. This variation did not affect its nuclear localization activity. Thus, there may be a significant advantage for the high Tat activity on subtype C replication.

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“…HIV-1 subtypes may exhibit phenotypic differences. Subtypes are believed to impact on tropism, with some studies associating increased CXCR4 usage with infections with subtype C (Johnston et al, 2003;Connell et al, 2008), and others finding decreased CXCR4 usage in subtype C infections (Bjorndal et al, 1997;Abebe et al, 1999;Peeters et al, 1999;Esbjornsson et al, 2010). Subtypes may have an important effect on transmission of HIV-1, as the subtype B was associated with homosexual transmission and the subtype C with heterosexual transmission (van Harmelen et al, 1997;van Harmelen et al, 2001), but a heterosexually driven subtype B epidemic has been observed in Trinidad and Tobago (Cleghorn et al, 2000).…”

Section: Introductionmentioning

confidence: 99%

Dearth of full-length HIV-1 sequences obscures the true HIV-1 genetic subtypes distribution in sub-Saharan Africa

Pondei¹,

Abdu²,

Orutugu³

2014

Afr. J. Biotechnol.

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HIV infection is still a public health problem in sub-Saharan Africa. The broad diversity exhibited by HIV-1 may impact on transmission, disease progression, drug resistance and vaccine development. Most analyses of HIV-1 subtype distribution have been on partial HIV-1 gene sequences, which may not adequately reflect the circulating subtypes. The objective of this study was to estimate the HIV-1 subtype distribution in sub-Saharan Africa using only full-length genome sequences. Using available HIV-1 full-length genome sequences from sub-Saharan Africa, the HIV-1 distribution in the region was analysed and compared with a previous global analysis which was not based entirely on full-length sequences. A total of 934 HIV-1 full-length genome sequences were available from 27 sub-Saharan countries. There was a disproportionate distribution of HIV-1 subtypes among countries with Cameroon having all the four HIV-1 groups. The subtype C was the most available in addition to a large proportion of circulating and unique recombinant forms (CRFs/URFs) especially in Central and West African countries, with frequencies of 32.6 to 90%. There was decreased representation of subtypes A and G in regions where CRFs/URFs were common compared with previous analysis using partial sequences. There is a need for more HIV-1 full-length genome sequences from sub-Saharan Africa for the true distribution of HIV-1 subtypes to be known, as analysis of partial sequences is not truly representative of the circulating subtypes.

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HIV-1 subtype C syncytium- and non-syncytium-inducing phenotypes and coreceptor usage among Ethiopian patients with AIDS

Abstract: Ethiopian patients with HIV-1 C-subtype AIDS harbour a remarkably low frequency of SI phenotype viruses. Coreceptor usage of these viruses correlates with their biological phenotypes.

Cited by 150 publications

References 32 publications

N-Linked Glycosylation of the HIV Type-1 gp120 Envelope Glycoprotein as a Major Determinant of CCR5 and CXCR4 Coreceptor Utilization

N-Linked Glycosylation of the HIV Type-1 gp120 Envelope Glycoprotein as a Major Determinant of CCR5 and CXCR4 Coreceptor Utilization

Human Immunodeficiency Virus Type 1 Subtype C Exhibits Higher Transactivation Activity of Tat than Subtypes B and E

Dearth of full-length HIV-1 sequences obscures the true HIV-1 genetic subtypes distribution in sub-Saharan Africa

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