Genetic Diversity and High Proportion of Intersubtype Recombinants among HIV Type 1-Infected Pregnant Women in Kisumu, Western Kenya

Division of AIDS, STD, and TB Laboratory Research, National Center for HIV, STD and TB prevention, Centers for Disease Control and Prevention, Atlanta, Georgia 30333, USA.
AIDS Research and Human Retroviruses (Impact Factor: 2.33). 06/2004; 20(5):565-74. DOI: 10.1089/088922204323087822
Source: PubMed


The high genetic diversity of HIV-1 continues to complicate effective vaccine development. To better understand the extent of genetic diversity, intersubtype recombinants and their relative contribution to the HIV epidemic in Kenya, we undertook a detailed molecular epidemiological investigation on HIV-1-infected women attending an antenatal clinic in Kisumu, Kenya. Analysis of gag-p24 region from 460 specimens indicated that 310 (67.4%) were A, 94 (20.4%) were D, 28 (6.1%) were C, 9 (2.0%) were A2, 8 (1.7%) were G, and 11 (2.4%) were unclassifiable. Analysis of the env -gp41 region revealed that 326 (70.9%) were A, 85 (18.5%) D, 26 (5.7%) C, 9 (2.0%) each of A2 and G, 4(0.9%) unclassifiable, and 1 (0.2%) CRF02_AG. Parallel analyses of the gag-p24 and env-gp41 regions indicated that 344 (74.8%) were concordant subtypes, while the remaining 116 (25.2%) were discordant subtypes. The most common discordant subtypes were D/A (40, 8.7%), A/D (27, 5.9%), C/A (11, 2.4%), and A/C (8, 1.7%). Further analysis of a 2.1-kb fragment spanning the gag-pol region from 38 selected specimens revealed that 19 were intersubtype recombinants and majority of them were unique recombinant forms. Distribution of concordant and discordant subtypes remained fairly stable over the 4-year period (1996-2000) studied. Comparison of amino acid sequences of gag-p24 and env-gp41 regions with the subtype A consensus sequence or Kenyan candidate vaccine antigen (HIVA) revealed minor variations in the immunodominant epitopes. These data provide further evidence of high genetic diversity, with subtype A as the predominant subtype and a high proportion of intersubtype recombinants in Kenya.

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Available from: Dale J. Hu, Apr 07, 2015
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    • "Subtype C reaches high prevalence in Burundi (>80%) [9], [10], Djibouti (>70%) [11] and Ethiopia (>95%) [12], [13], [14], [15], medium prevalence in Tanzania (20–40%) [16], [17], [18], [19], [20], and relatively low prevalence in Rwanda (14%) [21] and Uganda (<5%) [22], [23], [24], [25], [26], [27], [28]. Subtype C also accounts for a minor fraction (<15%) of HIV infections in western [29], [30], [31], coastal [28], [32], [33], [34] and central [28], [35], [36], [37] regions of Kenya; but displays a much higher frequency (25–50%) in some cities of the northern region that borders Ethiopia [38], [39]. "
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    ABSTRACT: The HIV-1 subtype C accounts for an important fraction of HIV infections in east Africa, but little is known about the genetic characteristics and evolutionary history of this epidemic. Here we reconstruct the origin and spatiotemporal dynamics of the major HIV-1 subtype C clades circulating in east Africa. A large number (n = 1,981) of subtype C pol sequences were retrieved from public databases to explore relationships between strains from the east, southern and central African regions. Maximum-likelihood phylogenetic analysis of those sequences revealed that most (>70%) strains from east Africa segregated in a single regional-specific monophyletic group, here called C(EA). A second major Ethiopian subtype C lineage and a large collection of minor Kenyan and Tanzanian subtype C clades of southern African origin were also detected. A bayesian coalescent-based method was then used to reconstruct evolutionary parameters and migration pathways of the C(EA) African lineage. This analysis indicates that the C(EA) clade most probably originated in Burundi around the early 1960s, and later spread to Ethiopia, Kenya, Tanzania and Uganda, giving rise to major country-specific monophyletic sub-clusters between the early 1970s and early 1980s. The results presented here demonstrate that a substantial proportion of subtype C infections in east Africa resulted from dissemination of a single HIV local variant, probably originated in Burundi during the 1960s. Burundi was the most important hub of dissemination of that subtype C clade in east Africa, fueling the origin of new local epidemics in Ethiopia, Kenya, Tanzania and Uganda. Subtype C lineages of southern African origin have also been introduced in east Africa, but seem to have had a much more restricted spread.
    PLoS ONE 07/2012; 7(7):e41904. DOI:10.1371/journal.pone.0041904 · 3.23 Impact Factor
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    • "Based on the example of the S1/S2 structure (Galetto et al. 2004), one might predict that a recombination hot spot could be found within our proposed structure (Galetto et al. 2006). Recombination breakpoints have been found in nucleotide region 230–330, i.e., in the sequence that folds to the predicted structure, between the pol gene sequences from different subtypes, such as between subtypes A and B, A and D, and B and D, as well as between B and F (Quarleri et al. 2004; Yang et al. 2004; Sa Filho et al. 2005). However, the existence of breakpoints in this region is insufficient to define a recombination hot spot. "
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    ABSTRACT: RNA secondary structures play several important roles in the human immunodeficiency virus (HIV) life cycle. To assess whether RNA secondary structure might affect the function of the HIV protease and reverse transcriptase genes, which are the main targets of anti-HIV drugs, we applied a series of different computational approaches to detect RNA secondary structures, including thermodynamic RNA folding predictions, synonymous variability analysis, and covariance analysis. Each method independently revealed strong evidence of a novel RNA secondary structure at the junction of the protease and reverse transcriptase genes, consisting of a 107-nucleotide region containing three stems, A, B, and C. First, RNA folding calculations by mfold and RNAfold both predicted the secondary structure with high confidence. Moreover, the same structure was predicted in a diverse set of reference sequences in HIV-1 group M, indicating that it is conserved across this group. Second, the predicted base-pairing regions displayed markedly reduced synonymous variation (approximately threefold lower than average) in a data set of 20,000 HIV-1 subtype B sequences from clinical samples. Third, independent analysis of covariation between synonymous mutations in this data set identified 10 covariant mutation pairs forming two diagonals that corresponded exactly to the sites predicted to base-pair in stems A and B. Finally, this structure was validated experimentally using selective 2'-hydroxyl acylation and primer extension (SHAPE). Discovery of this novel secondary structure suggests many directions for further functional investigation.
    RNA 11/2008; 14(12):2478-88. DOI:10.1261/rna.1252608 · 4.94 Impact Factor
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    • "Neighboring regions of Tanzania also have high subtype C prevalence [134] [145] [280] [330]. In contrast, subtype A maintains a 70% prevalence in Kenya [112] [134] [197] [243], with most remaining cases being unique recombinants [91] [197] [280] [330]. Uganda, which borders Tanzanina, Kenya and the DRC has more significant diversity than its eastern neighbors with a high prevalence of A, D and recombinants [51] [247] [271] as well as lower rates of C, B and G [247] [334]. "
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    ABSTRACT: The devastating consequences of AIDS pandemic will probably only be controlled when a vaccine is developed that is safe, effective, affordable, and simple enough to permit implementation in developing countries where the impact of AIDS is most severe. However, the major obstacle for the control of the spread of AIDS lies in the diversity of HIV and its enormous evolutionary potential. Numerous HIV forms contribute to the AIDS pandemic. Two viral types (HIV-1 and HIV-2), numerous groups (M, N and O for HIV-1 and A through H for HIV-2) and numerous subtypes, sub-subtypes and circulating recombinant forms (CRF) have emerged during the last 50 years. At least nine different genetic HIV-1 subtypes and over 20 CRFs were defined within group M, which accounts for the majority of cases in the AIDS pandemic. Even though HIV-1 subtype C and A predominate globally, the other viral forms co-circulate all over the world and may have a major impact for the strategies of pandemic control. Here we discuss the distribution of these divergent viral forms worldwide and the potential consequences of such a tremendous viral diversity for diagnostic, monitoring, treatment and the development of an effective vaccine.
    Current HIV research 02/2007; 5(1):23-45. DOI:10.2174/157016207779316297 · 1.76 Impact Factor
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