Tulio de Oliveira | University of KwaZulu-Natal (original) (raw)
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Subtype A is one of the rare HIV-1 group M (HIV-1M) lineages that is both widely distributed thro... more Subtype A is one of the rare HIV-1 group M (HIV-1M) lineages that is both widely distributed throughout the world and persists at high frequencies in the Congo Basin (CB), the site where HIV-1M likely originated. This, together with its high degree of diversity suggests that subtype A is amongst the fittest HIV-1M lineages. Here we use a comprehensive set of published near full-length subtype A sequences and A-derived genome fragments from both circulating and unique recombinant forms (CRFs/URFs) to obtain some insights into how frequently these lineages have independently seeded HIV-1M sub-epidemics in different parts of the world. We do this by inferring when and where the major subtype A lineages and subtype A-derived CRFs originated. Following its origin in the CB during the 1940s, we track the diversification and recombination history of subtype A sequences before and during its dissemination throughout much of the world between the 1950s and 1970s. Collectively, the timings and numbers of detectable subtype A recombination and dissemination events, the present broad global distribution of the sub-epidemics that were seeded by these events, and the high prevalence of subtype A sequences within the regions where these sub-epidemics occurred, suggest that ancestral subtype A viruses V C The Author(s) (and particularly sub-subtype A1 ancestral viruses) may have been genetically predisposed to become major components of the present epidemic.
Recombination between different HIV-1 group M (HIV-1M) subtypes is a major contributor to the ong... more Recombination between different HIV-1 group M (HIV-1M) subtypes is a major contributor to the ongoing genetic diversification of HIV-1M. However, it remains unclear whether the different genome regions of recombinants are randomly inherited from the different subtypes. To elucidate this, we analysed the distribution within 82 circulating and 201 unique recombinant forms (CRFs/URFs), of genome fragments derived from HIV-1M Subtypes A, B, C, D, F, and G and CRF01_AE. We found that viruses belonging to the analysed HIV-1M subtypes and CRF01_AE contributed certain genome fragments more frequently during recombination than other fragments. Furthermore, we identified statistically significant hot-spots of Subtype A sequence inheritance in genomic regions encoding portions of Gag and Nef, Subtype B in Pol, Tat and Env, Subtype C in Vif, Subtype D in Pol and Env, Subtype F in Gag, Subtype G in Vpu-Env and Nef, and CRF01_AE inheritance in Vpu and Env. The apparent non-randomness in the frequencies with which different subtypes have contributed specific genome regions to known HIV-1M recombinants is consistent with selection strongly impacting the survival of intersubtype recombinants. We propose that hotspots of genomic region inheritance are likely to demarcate the locations of subtype-specific adaptive genetic variations.
Genome Detective is an easy to use web-based software application that assembles the genomes of v... more Genome Detective is an easy to use web-based software application that assembles the genomes of viruses quickly and accurately. The application uses a novel alignment method that constructs genomes by reference-based linking of de-novo contigs by combining amino-acids and nucleotide scores. The software was optimized using synthetic datasets to represent the great diversity of virus genomes. The application was then validated with next generation sequencing data of hundreds of viruses. User time is minimal and it is limited to the time required to upload the data.
Subtype A is one of the rare HIV-1 group M (HIV-1M) lineages that is both widely distributed thro... more Subtype A is one of the rare HIV-1 group M (HIV-1M) lineages that is both widely distributed throughout the world and persists at high frequencies in the Congo Basin (CB), the site where HIV-1M likely originated. This, together with its high degree of diversity suggests that subtype A is amongst the fittest HIV-1M lineages. Here we use a comprehensive set of published near full-length subtype A sequences and A-derived genome fragments from both circulating and unique recombinant forms (CRFs/URFs) to obtain some insights into how frequently these lineages have independently seeded HIV-1M sub-epidemics in different parts of the world. We do this by inferring when and where the major subtype A lineages and subtype A-derived CRFs originated. Following its origin in the CB during the 1940s, we track the diversification and recombination history of subtype A sequences before and during its dissemination throughout much of the world between the 1950s and 1970s. Collectively, the timings and numbers of detectable subtype A recombination and dissemination events, the present broad global distribution of the sub-epidemics that were seeded by these events, and the high prevalence of subtype A sequences within the regions where these sub-epidemics occurred, suggest that ancestral subtype A viruses V C The Author(s) (and particularly sub-subtype A1 ancestral viruses) may have been genetically predisposed to become major components of the present epidemic.
Recombination between different HIV-1 group M (HIV-1M) subtypes is a major contributor to the ong... more Recombination between different HIV-1 group M (HIV-1M) subtypes is a major contributor to the ongoing genetic diversification of HIV-1M. However, it remains unclear whether the different genome regions of recombinants are randomly inherited from the different subtypes. To elucidate this, we analysed the distribution within 82 circulating and 201 unique recombinant forms (CRFs/URFs), of genome fragments derived from HIV-1M Subtypes A, B, C, D, F, and G and CRF01_AE. We found that viruses belonging to the analysed HIV-1M subtypes and CRF01_AE contributed certain genome fragments more frequently during recombination than other fragments. Furthermore, we identified statistically significant hot-spots of Subtype A sequence inheritance in genomic regions encoding portions of Gag and Nef, Subtype B in Pol, Tat and Env, Subtype C in Vif, Subtype D in Pol and Env, Subtype F in Gag, Subtype G in Vpu-Env and Nef, and CRF01_AE inheritance in Vpu and Env. The apparent non-randomness in the frequencies with which different subtypes have contributed specific genome regions to known HIV-1M recombinants is consistent with selection strongly impacting the survival of intersubtype recombinants. We propose that hotspots of genomic region inheritance are likely to demarcate the locations of subtype-specific adaptive genetic variations.
Genome Detective is an easy to use web-based software application that assembles the genomes of v... more Genome Detective is an easy to use web-based software application that assembles the genomes of viruses quickly and accurately. The application uses a novel alignment method that constructs genomes by reference-based linking of de-novo contigs by combining amino-acids and nucleotide scores. The software was optimized using synthetic datasets to represent the great diversity of virus genomes. The application was then validated with next generation sequencing data of hundreds of viruses. User time is minimal and it is limited to the time required to upload the data.