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Objective: To investigate the geographical origin and evolution dynamics of HIV-1 subtype C infection in India. Design: Ninety 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. Methods: Phylogenetic 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. Findings: The 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. Interpretation: Indian 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. [ABSTRACT FROM AUTHOR]

Abstract: Biologic and genetic differences between HIV-1 clade C in India and clade B in US suggest that the effect of anti-viral therapy in various body compartments may differ between these two clades. We examined the effect of therapy on viral loads in semen and blood of HIV-1-clade C infected subjects from India and evaluated whether HIV-1 in the semen is different from that in blood in these subjects. HIV-1 RNA was detected in semen and blood at all stages of the disease. Viral loads in semen and blood were strongly correlated with each other, but not with the CD4+ T cell count. Anti-viral treatment reduced viral load drastically in blood and semen within one month of post therapy. Genetic characterization of HIV-1 in the semen and blood demonstrated that they were highly compartmentalized. These data have important implications of sexual transmission of HIV-1 in clade C HIV-1 infected subjects. [Copyright &y& Elsevier]

Abstract: HIV-1 subtype C has been the predominant subtype throughout the course of the HIV-1 epidemic in India regardless of the geographic region of the country. In an effort to understand the mechanism of subtype C predominance in this country, we have investigated the in vitro replication fitness and transmission efficiency of HIV-1 subtypes A and C from India. Using a dual infection growth competition assay, we found that primary HIV-1 subtype C isolates had higher overall relative fitness in PBMC than subtype A primary isolates. Moreover, in an ex vivo cervical tissue derived organ culture, subtype C isolates displayed higher transmission efficiency across cervical mucosa than subtype A isolates. We found that higher fitness of subtype C was not due to a trans effect exerted by subtype C infected PBMC. A half genome A/C recombinant clone in which the 3′ half of the viral genome of subtype A was replaced with the corresponding subtype C3′ half, had similar replicative fitness as the parental subtype A. These results suggest that the higher replication fitness and transmission efficiency of subtype C virus compared to subtype A virus from India is most probably not due to the envelope gene alone and may be due to genes present within the 5′ half of the viral genome or to a more complex interaction between the genes located within the two halves of the viral genome. These data provide a model to explain the asymmetric distribution of subtype C over other subtypes in India. [Copyright &y& Elsevier]

A bipartite begomovirus was identified from a Boehmeria leiophylla plant sample exhibiting yellow mosaic symptoms collected in Nabanhe National Nature Reserve, Xishuangbanna, Yunnan, China. Five complete DNA-A and four DNA-B genome sequences were obtained by rolling-circle amplification (RCA), cloned, and sequenced. All DNA-A sequences were determined to be 2759 nucleotides in size, sharing 99.9%-100% nucleotide sequence identity with each other. The DNA-B sequences were comprised of 2673 nucleotides, sharing 98.6-100% nucleotide sequence identity with each other. Genomic organization of the begomovirus was typical of Old World bipartite begomoviruses. Sequence analysis revealed 81.84% nucleotide sequence identity to tomato leaf curl Hsinchu virus (ToLCHsV) from China for the DNA A component and 67.23% identity to the squash leaf curl China virus (SLCCNV) from India for the DNA B component. The sequence comparisons suggest that this bipartite begomovirus represents a novel species for which we propose the name "Ramie yellow mosaic virus".

Objective: To investigate the geographical origin and evolution dynamics of HIV-1 subtype C infection in India., Design: Ninety 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., Methods: Phylogenetic 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., Findings: The 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., Interpretation: Indian 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.

Background: Plasma viral load has been shown to be a meaningful prognostic marker for disease progression in untreated, HIV-1 subtype B-infected subjects in United States and Western Europe and therefore used as a prognostic marker for disease progression. Because of high expenses of commercially available viral load assays, the role of viral load in disease progression has not been evaluated in HIV-1 subtype C-infected patients in India., Methods: We developed an inexpensive real-time reverse transcriptase-polymerase chain reaction assay to quantify viral load in plasma of HIV-1 subtype C-infected subjects from India and used it in a longitudinal analysis of viral load and CD4 cell number in HIV-infected subjects from Calcutta, India., Results: The real-time reverse transcriptase-polymerase chain reaction assay can quantify plasma viral load with a linear range of detection from 10 to 10 HIV-1 RNA copies per input. Longitudinal analysis of viral load in a cohort of 39 subjects over an average period of approximately 3 years indicates that 1-log increase in HIV-1 RNA level was associated with a decline of 67 CD4 cell count. Furthermore, HIV-1 RNA level between 500 and 50,000 copies per milliliter would predict a 12.9% decrease in CD4 cell count per year, whereas HIV-1 RNA levels above 50,000 copies HIV-1 RNA per milliliter would predict a 25.3% decrease in CD4 cells per year. In addition, we estimated that the mean incubation period of disease development, as defined by the loss of CD4 below 200, is 8.2 years., Conclusion: Our report on the level of viral load on predicting CD4 decline in Indian subjects with HIV-1 provides an additional important tool to the physicians for treating and planning a therapeutic strategy to control HIV-1 infection in India.