TY - JOUR

T1 - Phylogenetic analysis of HIV-1 shows frequent cross-country transmission and local population expansions

AU - Bennedbæk, Marc

AU - Zhukova, Anna

AU - Tang, Man Hung Eric

AU - Bennet, Jaclyn

AU - Munderi, Paula

AU - Ruxrungtham, Kiat

AU - Gisslen, Magnus

AU - Worobey, Michael

AU - Lundgren, Jens D.

AU - Marvig, Rasmus L.

AU - the INSIGHT START study group

N1 - Funding Information: The primary funder of the START trial was NIAID (grant numbers UM1-AI068641, UM1-AI120197, and 1U01-AI136780). This study was made possible through a grant from the Danish National Research Foundation (grant number 126). Additional support was obtained from the National Institute of Allergy and Infectious Diseases, National Institutes of Health Clinical Center, National Cancer Institute, National Heart, Lung, and Blood Institute, Eunice Kennedy Shriver National Institute of Child Health and Human Development, National Institute of Mental Health, National Institute of Neurological Disorders and Stroke, National Institute of Arthritis and Musculoskeletal and Skin Diseases, Agence Nationale de Recherches sur le SIDA et les H?patites Virales (France), National Health and Medical Research Council (Australia), Bundesministerium f?r Bildung und Forschung (Germany), European AIDS Treatment Network, Medical Research Council (United Kingdom), National Institute for Health Research, National Health Service (United Kingdom), and University of Minnesota. Antiretroviral drugs were donated to the central drug repository by AbbVie, Bristol-Myers Squibb, Gilead Sciences, GlaxoSmithKline/ViiV Healthcare, Janssen Scientific Affairs, and Merck. M.W. was supported by NIH/NIAID R01AI084691. Publisher Copyright: © The Author(s) 2021. Published by Oxford University Press.

PY - 2021

Y1 - 2021

N2 - Understanding of pandemics depends on the characterization of pathogen collections from well-defined and demographically diverse cohorts. Since its emergence in Congo almost a century ago, Human Immunodeficiency Virus Type 1 (HIV-1) has geographically spread and genetically diversified into distinct viral subtypes. Phylogenetic analysis can be used to reconstruct the ancestry of the virus to better understand the origin and distribution of subtypes. We sequenced two 3.6-kb amplicons of HIV-1 genomes from 3,197 participants in a clinical trial with consistent and uniform sampling at sites across 35 countries and analyzed our data with another 2,632 genomes that comprehensively reflect the HIV-1 genetic diversity. We used maximum likelihood phylogenetic analysis coupled with geographical information to infer the state of ancestors. The majority of our sequenced genomes (n = 2,501) were either pure subtypes (A–D, F, and G) or CRF01_AE. The diversity and distribution of subtypes across geographical regions differed; USA showed the most homogenous subtype population, whereas African samples were most diverse. We delineated transmission of the four most prevalent subtypes in our dataset (A, B, C, and CRF01_AE), and our results suggest both continuous and frequent transmission of HIV-1 over country borders, as well as single transmission events being the seed of endemic population expansions. Overall, we show that coupling of genetic and geographical information of HIV-1 can be used to understand the origin and spread of pandemic pathogens.

AB - Understanding of pandemics depends on the characterization of pathogen collections from well-defined and demographically diverse cohorts. Since its emergence in Congo almost a century ago, Human Immunodeficiency Virus Type 1 (HIV-1) has geographically spread and genetically diversified into distinct viral subtypes. Phylogenetic analysis can be used to reconstruct the ancestry of the virus to better understand the origin and distribution of subtypes. We sequenced two 3.6-kb amplicons of HIV-1 genomes from 3,197 participants in a clinical trial with consistent and uniform sampling at sites across 35 countries and analyzed our data with another 2,632 genomes that comprehensively reflect the HIV-1 genetic diversity. We used maximum likelihood phylogenetic analysis coupled with geographical information to infer the state of ancestors. The majority of our sequenced genomes (n = 2,501) were either pure subtypes (A–D, F, and G) or CRF01_AE. The diversity and distribution of subtypes across geographical regions differed; USA showed the most homogenous subtype population, whereas African samples were most diverse. We delineated transmission of the four most prevalent subtypes in our dataset (A, B, C, and CRF01_AE), and our results suggest both continuous and frequent transmission of HIV-1 over country borders, as well as single transmission events being the seed of endemic population expansions. Overall, we show that coupling of genetic and geographical information of HIV-1 can be used to understand the origin and spread of pandemic pathogens.

KW - Ancestral State Reconstruction

KW - HIV

KW - Phylogenetics

KW - Phylogeography

KW - Transmission

U2 - 10.1093/ve/veab055

DO - 10.1093/ve/veab055

M3 - Journal article

C2 - 34532059

AN - SCOPUS:85116538034

VL - 7

JO - Virus Evolution

JF - Virus Evolution

SN - 2057-1577

IS - 2

M1 - A1347

ER -