A5018230858- HIV Research and Treatment
- SARS-CoV-2 and COVID-19 Research
- HIV/AIDS drug development and treatment
- SARS-CoV-2 detection and testing
- COVID-19 Clinical Research Studies
- HIV/AIDS Research and Interventions
- Bacillus and Francisella bacterial research
- Evolution and Genetic Dynamics
- Animal Genetics and Reproduction
- Parasitic Infections and Diagnostics
- Viral Infections and Immunology Research
- Research on Leishmaniasis Studies
- Mosquito-borne diseases and control
- Virology and Viral Diseases
- vaccines and immunoinformatics approaches
- Molecular Communication and Nanonetworks
- Respiratory viral infections research
- Evolutionary Game Theory and Cooperation
- Computational Drug Discovery Methods
- Viral Infections and Outbreaks Research
- Trypanosoma species research and implications
- Protein Structure and Dynamics
- COVID-19 epidemiological studies
- Viral gastroenteritis research and epidemiology
- Cytomegalovirus and herpesvirus research
Africa Health Research Institute
2017-2023
University of KwaZulu-Natal
2016-2020
Abstract The emergence of the SARS-CoV-2 variant concern Omicron (Pango lineage B.1.1.529), first identified in Botswana and South Africa, may compromise vaccine effectiveness lead to re-infections 1 . Here we investigated escape from neutralization by antibodies African individuals vaccinated with Pfizer BNT162b2. We used blood samples taken soon after vaccination who were previously infected or no evidence previous infection. isolated sequence-confirmed live virus an person observed that...
The emergence of SARS-CoV-2 Omicron, first identified in Botswana and South Africa, may compromise vaccine effectiveness the ability antibodies triggered by previous infection to protect against re-infection (1). Here we investigated whether Omicron escapes antibody neutralization Africans, either previously infected or uninfected, who were vaccinated with Pfizer BNT162b2. We also if requires ACE2 receptor infect cells. isolated sequence confirmed live virus from an person Africa compared...
Abstract SARS-CoV-2 variants of concern (VOC) have arisen independently at multiple locations and may reduce efficacy current vaccines targeted the spike glycoprotein. We re-cently described emergence VOC in South Africa (501Y.V2 or PANGO lineage B.1.351) with mutations receptor-binding domain (RBD) N-terminal (NTD). Here, using a live virus neutralization assay (LVNA), we compared first wave (B.1.1.117) versus 501Y.V2 variant plasma collected from adults hospitalized COVID-19 two African...
Abstract Omicron BA.2.86 subvariant differs from BA.2 as well recently circulating variants by over 30 mutations in the spike protein alone. Here we report on isolation of live a diagnostic swab collected South Africa which tested for escape neutralizing antibodies and viral replication properties cell culture. We found that does not have significantly more relative to XBB.1.5 immunity elicited either XBB-family infection or residual sera African population. extensive ancestral virus with...
The emergence of the SARS-CoV-2 variant concern Omicron (Pango lineage B.1.1.529), first identified in Botswana and South Africa, may compromise vaccine effectiveness lead to re-infections1. Here we investigated escape from neutralization by antibodies African individuals vaccinated with Pfizer BNT162b2. We used blood samples taken soon after vaccination who were previously infected or no evidence previous infection. isolated sequence-confirmed live virus an person observed that requires...
Cell-to-cell spread of HIV, a directed mode viral transmission, has been observed to be more rapid than cell-free infection. However, mechanism for earlier onset gene expression in cell-to-cell was previously uncharacterized. Here we used time-lapse microscopy combined with automated image analysis quantify the timing HIV fluorescent reporter cell line, as well single staining infection over time primary cells. We compared infection, and limited both types transmission two-hour window...
Abstract Viruses increase the efficiency of close-range transmission between cells by manipulating cellular physiology and behavior, SARS-CoV-2 uses cell fusion as one mechanism for cell-to-cell spread. Here we visualized infection using time-lapse microscopy a human lung line used live virus neutralization to determine sensitivity spread neutralizing antibodies. rapidly led fusion, forming multinucleated with clustered nuclei which started be detected at 6h post-infection. To compare...
Abstract One mechanism of variant formation may be evolution during long-term infection in immunosuppressed people. To understand the viral phenotypes evolved such infection, we tested SARS-CoV-2 viruses from an ancestral B.1 lineage lasting over 190 days post-diagnosis advanced HIV disease individual. Sequence and phylogenetic analysis showed two evolving sub-lineages, with second sub-lineage replacing first a seeming evolutionary sweep. Each independently escape neutralizing antibodies....
HIV has been reported to be cytotoxic in vitro and lymph node infection models. Using a computational approach, we found that partial inhibition of transmissions multiple virions per cell could lead increased numbers live infected cells. If the number viral DNA copies remains above one after inhibition, then eliminating surplus reduces death. line, observed cells when was partially inhibited with antiretroviral efavirenz or neutralizing antibody. We used at concentrations nodes inhibit by...
Abstract The milder clinical manifestations of Omicron infection relative to pre-Omicron SARS-CoV-2 raises the possibility that extensive evolution results in reduced pathogenicity. To test this hypothesis, we quantified induction cell fusion and death evolved from ancestral virus during long-term infection. Both were BA.1 virus. Evolved was isolated at different times a 6-month an immunosuppressed individual with advanced HIV disease. 16 days post-reported symptom onset induced fusogenicity...
Abstract HIV exists as multiple genotypes in a single infected individual referred to quasispecies. Here we reproduced quasispecies by moderate selective pressure using an reverse transcriptase inhibitor. The drug resistant genotype never completely supplanted the sensitive genotype, which stabilized at about 20 percent of viral sequences. Single-cell sequencing showed that frequency plateaued when cells were co-infected with and genotypes, suggesting sharing proteins (complementation) masks...
Abstract HIV has been reported to be cytotoxic in vitro and lymph node infection models. Using a computational approach, we found that partial inhibition of transmission which involves multiple virions per cell could lead increased numbers live infected cells if the number viral DNA copies remains above one after inhibition, as eliminating surplus reduces death. line, observed when was partially inhibited with antiretroviral efavirenz or neutralizing antibody. We then used at concentrations...