Browsing by Author "Varathan, Olivette"

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    The effect of childhood trauma, ApoE genotype and HIV-1 viral protein R variants on change in cognitive performance
    (BMC (part of Springer Nature), 2019-12-27) Womersley, Jacqueline S.; Clauss, Lara B.; Varathan, Olivette; Engelbrecht, Susan; Hemmings, Sian M. J.; Seedat, Soraya; Spies, Georgina
    Objective: Gene–environment interactions contribute to the development of HIV-associated neurocognitive disorders. We examined whether childhood trauma, apolipoprotein E isoforms and viral protein R (Vpr) variants were associated with change in cognitive performance. Seventy-three seropositive women completed neuropsychological assessments at baseline and 1-year follow-up. We conducted genetic analyses using DNA obtained from blood and calculated risk scores based on Vpr amino acid 37, 41 and 55 variants that were previously associated with cognitive performance. Results: Global cognitive scores declined significantly over the 1-year study period (p = 0.029). A reduction in global cognitive scores was associated with childhood trauma experience (p = 0.039).
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    Molecular characterisation of HIV-1 recombinants and non-subtype C viruses in South Africa
    (Stellenbosch : Stellenbosch University, 2019-03) Varathan, Olivette; Jacobs, Graeme Brendon; Engelbrecht, Susan; Stellenbosch University. Faculty of Medicine and Health Sciences. Dept. of Pathology. Medical Virology.
    ENGLISH ABSTRACT: HIV/AIDS is a severe health burden, affecting 36.9 million people worldwide by the end of 2017. South Africa has the largest HIV-1 epidemic in the world, estimated at 7.2 million infected individuals by the end of 2017. The HIV-1 epidemic in South Africa is dominated by HIV-1 subtype C, accounting for an estimated 98.2% of the infections in the country, based on the viral sequences in the Los Alamos National Library (LANL) database. To date, to the best of our knowledge, 22 papers have been published on non-subtype C viruses in South Africa. This study aimed to characterise two near full-length genome sequences of non-subtype C viruses in South Africa. The study samples were obtained through the diagnostic services of the National Health Laboratory Services (NHLS), performing routine drug resistance testing within the Division of Medical Virology, Stellenbosch University. All samples received were sequenced in the partial pol region (~1.4kb) of the viral genome by the NHLS. The possible subtype of the virus was identified from the sequences using online subtyping programmes. All sequences and samples that identified as possible non-subtype C viruses were recorded in a separate non-subtype C cohort. In 2011, a possible C, D recombinant virus was first identified in this cohort. By the end of 2015, 30 similar recombinant viruses were observed in the cohort, indicating a possible emergence of this recombinant strain. Two of the samples that identified as possible C, D recombinants were selected for further near full-length genome (NFLG) characterisation. Proviral DNA, from sample EC148, was extracted from PBMCs and viral RNA, from sample WC416, was extracted from plasma. The RNA was reverse transcribed to DNA via cDNA synthesis. Both sample viruses were amplified by PCR in two rounds. The first round targeted the amplification of the HIV-1 NFLG (8978bp) and the second targeted the amplification of two overlapping fragments (5455bp and 4909bp). Positive PCR amplicons were purified and sequenced. The generated sequences were read and analysed before being used in online subtyping programmes. The jumping profile hidden markov model (jpHMM), REGA and recombination identification programmes (RIP) were used to preliminary assign subtypes to both samples. Phylogenetic analyses was inferred to confirm / reject the online subtyping programme results. Online subtyping programmes identified the virus sequences of samples EC148 and WC416 as complex A, C, D recombinants. Phylogenetic analysis confirmed the online subtyping programme results for the sequence of sample WC416 in identifying it as a complex A, C, D recombinant. Phylogenetic analysis indicated that the sequence of sample EC148 is consistent with the results observed from the online subtyping programmes. Each HIV-1 sequence identified as a unique complex recombinant form as the breakpoints between the different subtypes differed. The emergence of new and unique non-subtype C recombinants in South Africa indicates that the epidemic is complex and evolving. It is therefore important to monitor the spread of different HIV subtypes circulating in South Africa.