Search Abstracts

Background Persistent infection with SARS-CoV-2 is hypothesised to give rise to new variants of concern (VoCs). However, sequencing methods to investigate intrahost variation are limited: short-read technology precludes haplotyping, and long-read technology has high error rates. We describe a new method for investigating SARS-CoV-2 quasispecies and apply it to identify divergent spike haplotypes arising during…

Background Upon entry into a cell, the HIV core plays a pivotal part in many of the interactions that lead to successful viral replication. The HIV core has evolved to interact with proteins necessary for replication and evade proteins that inhibit replication. We aim to characterize the mechanisms of capsid (CA) recognition by known and…

Background Fostemsavir (FTR), approved by the FDA in July 2020, is a first-in-class small molecule for treating multi-drug resistant HIV-1 infection. It is the prodrug of its active form, temsavir (TMR). TMR is classified as an attachment inhibitor and is thought to stabilize a native state of HIV Env, the state recognized by most broadly…

Background Human immunodeficiency virus (HIV) is the result of the cross-species transmission of simian immunodeficiency viruses (SIVs) that endemically infect non-human primates. While pandemic HIV-1 M is the result of a chimpanzee lentivirus (SIVcpz) cross-species transmission to humans, lentiviruses from other non-human primates have also spilled over into humans. Since the emergence of HIV, the…

Background Intra-host evolution reflects a general mechanism for the continued emergence of novel highly divergent SARS-CoV-2 variants. The intra-host evolution of SARS-CoV-2 was investigated with the aim of assessing conditions associated with the acquisition of new viral mutations through the sequencing of viral genomes. Methods 58 cases of COVID-19 with 2 or more longitudinally positive…

Background Recent studies characterizing primary isolates of HIV-1 from acute timepoints, rebound after treatment interruption, chronic viremia, and the persistent reservoir have identified key phenotypic differences between these viruses when replicating in primary CD4 T cells. Here, we leverage these HIV-1 isolates to probe effects of virus clade, isolate origin, and cell donor sex on…

Background CD4+ T-cell recovery varies among people with HIV (PWH) who are virologically suppressed on antiretroviral therapy (ART). Our objective was to identify the genetic predictors of CD4 recovery measured by the slope of longitudinal CD4+ T-cell counts within two years after ART initiation in PWH virologically suppressed on ART. We hypothesized that select single…

Background Humans and nonhuman primates (NHPs) possess seven APOBEC3 (A3) enzymes, which restrict various viruses, notably HIV in humans and SIV in NHPs. These antiviral proteins inhibit viral infection by inducing G>A mutations in viral genomes and/or through mutation-independent mechanisms. HIV and SIV counteract A3 enzymes via their virion infectivity factor (Vif), which promotes A3…

Background HIV-1 infection commonly causes multiple hematopoietic abnormalities, known as pancytopenia, including lymphopenia, anemia, granulocytopenia, and thrombocytopenia, suggesting a central deficiency in bone marrow hematopoiesis. However, the mechanism by which HIV-1 infection leads to bone marrow hematopoietic defects remains unknown due to the lack of appropriate in vivo models. In this study, we established a…

Background Acute SARS-CoV-2 infections are mostly cleared within a few days but can become chronic in immunocompromised individuals. Impaired immune clearance is also thought to be a major factor in the evolution of new SARS-CoV-2 variants of concern(VOC). However, it is unclear how intra-host variation accumulates over the course of very long-term chronic SARS-CoV-2 infection,…