Higher sequence diversity in the vaginal tract than in blood at early HIV-1 infection

Autor:	Korey Demers, Charles S. Morrison, Eric J. Arts, Marshall Munjoma, Peter Mugyenyi, Josaphat Byamugisha, Gabrielle Nickel, Pai Lien Chen, Robert A. Salata, Art F. Y. Poon, Fred Kyeyune, Cynthia Kwok, Katja Klein, Tsungai Chipato, Immaculate Nankya, Emmanuel Ndashimye, Sandra Rwambuya
Jazyk:	angličtina
Rok vydání:	2018
Předmět:	0301 basic medicine RNA viruses Physiology Artificial Gene Amplification and Extension HIV Infections Cervix Uteri Pathology and Laboratory Medicine Genetic analysis Polymerase Chain Reaction Reproductive Tract Infections law.invention Cohort Studies White Blood Cells Immunodeficiency Viruses law Animal Cells Blood plasma Genotype HIV Seropositivity Medicine and Health Sciences Uganda Longitudinal Studies Biology (General) Polymerase chain reaction env Gene Products Human Immunodeficiency Virus High-Throughput Nucleotide Sequencing Viral Load 3. Good health Body Fluids medicine.anatomical_structure Blood Medical Microbiology Viral Pathogens Viruses Vagina RNA Viral Female Pathogens Anatomy Cellular Types Research Article Zimbabwe QH301-705.5 Immune Cells 030106 microbiology Immunology Viremia Biology Research and Analysis Methods Microbiology Virus Blood Plasma 03 medical and health sciences Virology Retroviruses medicine Genetics Humans T Helper Cells Molecular Biology Techniques Microbial Pathogens Molecular Biology Genetic diversity Blood Cells Base Sequence Lentivirus Organisms Biology and Life Sciences HIV Genetic Variation Human Genetics Cell Biology RC581-607 medicine.disease 030104 developmental biology HIV-1 Parasitology Immunologic diseases. Allergy Cloning
Zdroj:	PLoS Pathogens, Vol 14, Iss 1, p e1006754 (2018) PLoS Pathogens
ISSN:	1553-7374 1553-7366
Popis:	In the majority of cases, human immunodeficiency virus type 1 (HIV-1) infection is transmitted through sexual intercourse. A single founder virus in the blood of the newly infected donor emerges from a genetic bottleneck, while in rarer instances multiple viruses are responsible for systemic infection. We sought to characterize the sequence diversity at early infection, between two distinct anatomical sites; the female reproductive tract vs. systemic compartment. We recruited 72 women from Uganda and Zimbabwe within seven months of HIV-1 infection. Using next generation deep sequencing, we analyzed the total genetic diversity within the C2-V3-C3 envelope region of HIV-1 isolated from the female genital tract at early infection and compared this to the diversity of HIV-1 in plasma. We then compared intra-patient viral diversity in matched cervical and blood samples with three or seven months post infection. Genetic analysis of the C2-V3-C3 region of HIV-1 env revealed that early HIV-1 isolates within blood displayed a more homogeneous genotype (mean 1.67 clones, range 1–5 clones) than clones in the female genital tract (mean 5.7 clones, range 3–10 clones) (p Author summary During chronic HIV-1 infection, high viral diversity can be found in the blood and semen of donors. However, a single HIV-1 clone establishes productive infection in the recipient following heterosexual transmission. To investigate the genetic bottleneck occurring at the earliest stages of heterosexual HIV-1 transmission, we characterized the HIV-1 envelope sequence diversity at very early and early stages of infection in the female reproductive tract and matched plasma samples from a cohort of Ugandan and Zimbabwean women. A more diverse viral population was observed in the endocervical swab samples compared to plasma. Endocervical samples harbored a larger number of viral clones, while in the majority of plasma samples only a single clone was present early in infection. Interestingly, these observations were independent of HIV-1 subtype, hormonal contraceptive use or the number of sex acts and partners. Furthermore, in the cases of higher HIV-1 diversity in the blood during early infection, faster CD4 T cell decline were observed during chronic disease suggesting faster disease progression. Our findings provide novel in vivo evidence for the existence of an intra-patient genetic bottleneck restricting the HIV-1 from the vaginal tract to the blood during early heterosexual HIV-1 transmission.
Databáze:	OpenAIRE
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