Long-read deep sequencing reveals high rates of multilineage transmission and rapid viral population changes in acute HIV infection
Abstract
Abstract Understanding the selective forces acting upon HIV early in infection is crucial to design prevention strategies. By leveraging deep sequencing and the short diagnostic intervals of the FRESH and RV217 cohorts between the last-negative and first-positive RNA tests (median 4 days), we captured a precise and early snapshot of acute HIV infection. The frequency of multiple transmitted viruses of 37% in these as well as placebo recipients from the AMP trials (NCT02716675 and NCT02568215) was higher than previously published, with the true frequency likely to be higher. The relative abundance of lineages fluctuated substantially over time in two-thirds of the multilineage infections, generating uncertainty in identifying the specific viruses that were transmitted and founding the infection. At the population level, viral populations exhibited limited diversity and selection on the Gag and Env proteins at the earliest times examined, with sites inferred to be undergoing negative selection most evident. These data may help explain vaccination failures and provide new targets for prevention.
Article Details
Authors (35)
James I. Mullins
Wenjie Deng
Elena E. Giorgi
Vaccine and Infectious Diseases Division, Fred Hutchinson Cancer Center
Craig A. Magaret
Morgane Rolland
U.S. Military HIV Research Program, Center for Infectious Disease Research, Walter Reed Army Institute of Research
Tanmoy Bhattacharya
Dylan H. Westfall
Infectious Disease Division, Fred Hutchinson Cancer Center
Anna E. J. Yssel
Roger E. Bumgarner
Ben Murrell
Thumbi Ndung’u
Human Immunodeficiency Virus, Pathogenesis Programme, Doris Duke Medical Research Institute, Nelson R Mandela School of Medicine, University of KwaZulu-Natal
Merlin L. Robb
Raabya Rossenkhan
Paul T. Edlefsen
Krista L. Dong
Lennie Chen
Asanda Gwashu-Nyangiwe
Hong Zhao
Ruwayhida Thebus
Nonkululeko Ndabambi
Bruna Galvao
Fredrick Sawe
Sorachai Nitayaphan
Talita York
David Matten
Hugh Murrell
Alec P. Pankow
Michal Juraska
James Ludwig
John Hural
Myron S. Cohen
Lawrence Corey
Vaccine and Infectious Disease Division, Fred Hutchinson Cancer Center
M. Juliana McElrath
Vaccine and Infectious Disease Division, Fred Hutchinson Cancer Center
Peter B. Gilbert
Carolyn Williamson