Absence of Coreceptor Switch with Disease Progression in Human Immunodeficiency Virus Infections in India

Cecilia, D.; Kulkarni, Smita; Tripathy, Srikanth; Gangakhedkar, Raman; Paranjape, Ramesh; Gadkari, Deepak A.

doi:10.1006/viro.2000.0297

Cited by 123 publications

(87 citation statements)

References 24 publications

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“…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).…”

mentioning

confidence: 84%

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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“…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).…”

mentioning

confidence: 84%

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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“…CXCR4 is more widely expressed on different CD4 ϩ T-cell populations compared to CCR5, and X4 viruses thus have a broader T-cell tropism (3,26). Nevertheless, CD4 depletion and AIDS occur in patients from whom only CCR5-using viruses can be isolated (6,10). Transmitted viruses are usually CCR5-using (R5) viruses, and individuals homozygous for a defective CCR5 gene (⌬32 CCR5) are substantially protected from infection (5).…”

mentioning

confidence: 99%

Non-Macrophage-Tropic Human Immunodeficiency Virus Type 1 R5 Envelopes Predominate in Blood, Lymph Nodes, and Semen: Implications for Transmission and Pathogenesis

Peters

Sullivan

Dueñas-Decamp

et al. 2006

J Virol

188

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Human immunodeficiency virus type 1 (HIV-1) R5 isolates that predominantly use CCR5 as a coreceptor are frequently described as macrophage tropic. Here, we compare macrophage tropism conferred by HIV-1 R5 envelopes that were derived directly by PCR from patient tissue. This approach avoids potentially selective culture protocols used in virus isolation. Envelopes were amplified (i) from blood and semen of adult patients and (ii) from plasma of pediatric patients. The phenotypes of these envelopes were compared to those conferred by an extended panel of envelopes derived from brain and lymph node that we reported previously. Our results show that R5 envelopes vary by up to 1,000-fold in their capacity to confer infection of primary macrophages. Highly macrophage-tropic envelopes were predominate in brain but were infrequent in semen, blood, and lymph node samples. We also confirmed that the presence of N283 in the C2 CD4 binding site of gp120 is associated with HIV-1 envelopes from the brain but absent from macrophage-tropic envelopes amplified from blood and semen. Finally, we compared infection of macrophages, CD4 ؉ T cells, and peripheral blood mononuclear cells (PBMCs) conferred by macrophage-tropic and non-macrophage-tropic envelopes in the context of full-length replication competent viral clones. Non-macrophage-tropic envelopes conferred low-level infection of macrophages yet infected CD4؉ T cells and PBMCs as efficiently as highly macrophage-tropic brain envelopes. The lack of macrophage tropism for the majority of the envelopes amplified from lymph node, blood, and semen is striking and contrasts with the current consensus that R5 primary isolates are generally macrophage tropic. The extensive variation in R5 tropism reported here is likely to have an important impact on pathogenesis and on the capacity of HIV-1 to transmit.

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“…Group M is further divided into 10 phylogenically related genetic subtypes (clades A, B, C, D, F1, F2, G, H, J, and K) that, together with a growing number of circulating intersubtype recombinant forms, comprise the majority of HIV-1 variants in the world today. Clade C is emerging as most prevalent, being common in India (15,16,31,41) and the southern African countries of Botswana, Zimbabwe, Malawi, Mozambique, and South Africa (7,8,25,26,60,64,79,81). Clade B is dominant in North America and Western Europe and has been a major focus for vaccine development (27).…”

mentioning

confidence: 99%

Regional Clustering of Shared Neutralization Determinants on Primary Isolates of Clade C Human Immunodeficiency Virus Type 1 from South Africa

Bures

Morris²,

Williamson

et al. 2002

J Virol

113

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Absence of Coreceptor Switch with Disease Progression in Human Immunodeficiency Virus Infections in India

Cited by 123 publications

References 24 publications

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

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

Non-Macrophage-Tropic Human Immunodeficiency Virus Type 1 R5 Envelopes Predominate in Blood, Lymph Nodes, and Semen: Implications for Transmission and Pathogenesis

Regional Clustering of Shared Neutralization Determinants on Primary Isolates of Clade C Human Immunodeficiency Virus Type 1 from South Africa

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