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Characterization of HIV-1 diversity in various compartments at the time of primary infection by ultradeep sequencing.

ABSTRACT: We used next-generation sequencing to evaluate the quantity and genetic diversity of the HIV envelope gene in various compartments in eight patients with acute infection. Plasma (PL) and seminal fluid (SF) were available for all patients, whole blood (WB) for seven, non-spermatozoid cells (NSC) for four, and saliva (SAL) for three. Median HIV-1 RNA was 6.2 log10 copies/mL [IQR: 5.5-6.95] in PL, 4.9 log10 copies/mL [IQR: 4.25-5.29] in SF, and 4.9 log10 copies/mL [IQR: 4.46-5.09] in SAL. Median HIV-1 DNA was 4.1 log10 copies/106 PBMCs [IQR: 3.15-4.15] in WB and 2.6 log10 copies /106 Cells [IQR: 2.23-2.75] in NSC. The median overall diversity per patient varied from 0.0005 to 0.0232, suggesting very low diversity, confirmed by the clonal aspect of most of the phylogenetic trees. One single haplotype was present in all compartments for five patients in the earliest stage of infection. Evidence of higher diversity was established for two patients in PL and WB, suggesting compartmentalization. Our study shows low diversity of the env gene in the first stages of infection followed by the rapid establishment of cellular reservoirs of the virus. Such clonality could be exploited in the search for early patient-specific therapeutic solutions.

SUBMITTER: Gaube G

PROVIDER: S-EPMC7016127 | biostudies-literature | 2020 Feb

REPOSITORIES: biostudies-literature

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Characterization of HIV-1 diversity in various compartments at the time of primary infection by ultradeep sequencing.

Gaube Géraldine G Armero Alix A Salmona Maud M Néré Marie-Laure ML Mahjoub Nadia N Lascoux-Combe Caroline C Gabassi Audrey A Gallien Sébastien S Amara Ali A Molina Jean Michel JM Delaugerre Constance C Chaix Marie-Laure ML

Scientific reports 20200212 1

We used next-generation sequencing to evaluate the quantity and genetic diversity of the HIV envelope gene in various compartments in eight patients with acute infection. Plasma (PL) and seminal fluid (SF) were available for all patients, whole blood (WB) for seven, non-spermatozoid cells (NSC) for four, and saliva (SAL) for three. Median HIV-1 RNA was 6.2 log10 copies/mL [IQR: 5.5-6.95] in PL, 4.9 log10 copies/mL [IQR: 4.25-5.29] in SF, and 4.9 log10 copies/mL [ ...[more]

PMID: 32051463

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Project description:The parasitic nematode intestine is responsible for nutrient digestion and absorption, and many other processes essential for reproduction and survival, making it a valuable target for anthelmintic drug treatment. However, nematodes display extreme biological diversity (including occupying distinct trophic habitats), resulting in limited knowledge of intestinal cell/protein functions of fundamental or adaptive significance. We developed a perfusion model for isolating intestinal proteins in Ascaris suum (a parasite of humans and swine), allowing for the identification of over 1000 intestinal A. suum proteins (using mass spectrometry), which were assigned to several different intestinal cell compartments (intestinal tissue, the integral and peripheral intestinal membranes, and the intestinal lumen). A multi-omics analysis approach identified a large diversity of biological functions across intestinal compartments, based on both functional enrichment analysis (identifying terms related to detoxification, proteolysis, and host-parasite interactions) and regulatory binding sequence analysis to identify putatively active compartment-specific transcription factors (identifying many related to intestinal sex differentiation or lifespan regulation). Orthologs of A. suum proteins in 15 other nematodes species, five host species, and two outgroups were identified and analyzed. Different cellular compartments demonstrated markedly different levels of protein conservation; e.g. integral intestinal membrane proteins were the most conserved among nematodes (up to 96% conservation), whereas intestinal lumen proteins were the most diverse (only 6% conservation across all nematodes, and 71% with no host orthologs). Finally, this integrated multi-omics analysis identified conserved nematode-specific intestinal proteins likely performing essential functions (including V-type ATPases and ABC transporters), which may serve as promising anthelmintic drug or vaccine targets in future research. Collectively, the findings provide valuable new insights on conserved and adaptive features of nematode intestinal cells, membranes and the intestinal lumen, and potential targets for parasite treatment and control.

Dataset Information

Characterization of HIV-1 diversity in various compartments at the time of primary infection by ultradeep sequencing.

Publications

Characterization of HIV-1 diversity in various compartments at the time of primary infection by ultradeep sequencing.

Similar Datasets

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