HIV-1 subtypes and coreceptor usage in a population from Northern Kenya

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dc.contributor.authorMuriuki, John Martin
dc.date.accessioned2012-04-20T08:42:41Z
dc.date.available2012-04-20T08:42:41Z
dc.date.issued2012-04-20
dc.descriptionRA 643.86 .K4M87
dc.description.abstractHuman immunodeficiency virus type 1 (HIV-I) phenotype variability plays an important role in HIV-I transmission and pathogenesis of Acquired Immune Deficiency Syndrome (AIDS). The basis of heterogeneity is known to be the differential use of chemokine receptors as coreceptors for viral entry. Beta chemokine receptor 5 (CCR5) using variants are associated with acute infections, macrophage tropism, non-syncytium inducing (NSI) phenotype and slow progression to AIDS. Alpha chemokine receptor 4 (CXCR4) using variants evolve later in infection in about 50 % of the patients and are associated with T cell line tropism, syncytium induction, accelerated T cell depletion and rapid progression to AIDS. Determinants of coreceptor usage and biological phenotypes are mapped in the third variable region (V3) of the gp120 envelope gene. The aim of this study was to determine viral coreceptor usage in a population of HIV -I infected individuals in Northern Kenya and investigate presence of relationship with the specific HIV-l SUbtypes. In this study, 135 whole blood samples were collected from HIV -I positive patients in Northern Kenyan. Erythf()C)1es were lysed and proviral DNA extracted from lymphocytes using DNazol reagent and ethanol precipitation. The V3 region was amplified by nested PCR using C2V3 region specific primers. Amplicons were sequenced directly using Bigdye technology (sequencing kit from Applied Biosystems) to generate gpl20 sequences that were used to determine the HIV-l subtype after comparison with the Los Alamos reference sequences. Three Circulating HIV -l subtypes were observed in the following proportions; Subtype Al (54~{')., C (2~{,), D (10%) and 9% of these Subtypes recombinant Forms. The properties of these sequences, amino acid on certain key positions and their net charge, were analyzed by bioinformatics tools to determine coreceptorusage. CXCR4 usage was most predominant (69.2 %) compared to CCR5 (21.8 ~') and dual coreceptor (9.0 %) usage. Most infected patients were inferred to be in late stage of infection based on coreceptor usage data Coreceptor usage was observed to be strongly associated with HIV -I subtypes. From the observations in this study, specific HIV -I subtypes needs to be taken into consideration during HIV-I management and interpretation of coreceptor usage data. Sequences generated from HIV-strains circulating in Northern Kenya indicates high genomic divergence hence need to consider a cocktail of antigen in \'8CCine development and need to develop genomes analysis software based on locally circulating HIV -I subtypes.en_US
dc.description.sponsorshipKenyatta Universityen_US
dc.identifier.urihttp://ir-library.ku.ac.ke/handle/123456789/4159
dc.language.isoenen_US
dc.titleHIV-1 subtypes and coreceptor usage in a population from Northern Kenyaen_US
dc.typeThesisen_US
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