Metagenomic Sequencing of HIV-1 in the Blood and Female Genital Tract Reveals Little Quasispecies Diversity during Acute Infection

Abstract

Due to error-prone replication, HIV-1 generates a diverse population of viruses within a chronically infected individual. When HIV-1 is transmitted to a new individual, one or a few viruses establish the new infection, leading to a genetic bottleneck in the virus population. Understanding the timing and nature of this bottleneck may provide insight into HIV-1 vaccine design and other preventative strategies. We examined the HIV-1 population in three women enrolled in a unique prospective cohort in South Africa who were followed closely during the earliest stages of HIV-1 infection. We found very little HIV-1 diversity in the blood and female genital tract during the first 2 weeks after virus was detected in the bloodstream. These results are compatible with a very early HIV-1 population bottleneck, suggesting the need to study the HIV-1 population in the female genital tract before virus is detectable in the bloodstream.

Current Status of Latency Reversing Agents Facing the Heterogeneity of HIV-1 Cellular and Tissue Reservoirs

“…HIV-1 sequence diversity has been reported to be either higher (Klein et al, 2018) or similar (Piantadosi et al, 2019) to genital tract compared to blood. Viral compartmentalization between the blood and the male genital tract has been reported by multiple studies including SIV-infected macaques (Delwart et al, 1998;Paranjpe et al, 2002;Pillai et al, 2005;Coombs et al, 2006;Diem et al, 2008;Houzet et al, 2018).…”

Dynamics of HIV-1 quasispecies diversity of participants on long-term antiretroviral therapy based on intrahost single-nucleotide variations

“…The iSNV analysis, which differed from the previous method, used counts and relative frequencies of iSNVs to indicate intrahost viral diversity. In recent years, iSNVs have been widely used in studies of RNA viral quasispecies, such as influenza virus (Gorman et al, 2016), norovirus, Ebola virus (Ni et al, 2016), Dengue virus (Sim et al, 2015), yellow fever virus (Chen et al, 2018) and HIV (Piantadosi et al, 2019). In addition to reflection of intrahost dynamic changes at different infection stages, iSNV analysis can capture the differences between plasma RNA and cellular DNA.…”

“…Following primary infection, a population of viral variants, or quasispecies, becomes established in the host (Domingo and Perales, 2018). Historically, the viral population within an HIV-1infected individual has been represented by the sequences obtained from single-genome sequencing or the consensus sequence obtained from ultra-deep sequencing (UDS) (Piantadosi et al, 2019;Wymant et al, 2018), which may not show the low frequency variations that occur at each nucleotide site (Capoferri et al, 2019;Lorenzo-Redondo et al, 2017;Wagner et al, 2013Wagner et al, , 2014. However, to accommodate current epidemiological standards, more information can be obtained through UDS and quantification of intrahost single-nucleotide variations (iSNVs) (Yang et al, 2013).…”

Metagenomic sequencing to detect respiratory viruses in persons under investigation for COVID-19

“…Excess nasopharyngeal swab samples were retrieved within 72 hours of collection and underwent RNA extraction and SARS-CoV-2 testing by triplex RT-PCR (2). Samples underwent unbiased mNGS as previously described (3, 4). Briefly, this included DNAse treatment, random primer cDNA synthesis, Nextera XT tagmentation, and Illumina sequencing to a median depth of 35 million reads.…”