Open AccessEnvelope Vaccination Shapes Viral Envelope Evolution following Simian Immunodeficiency Virus Infection in Rhesus Monkeys
Author(s) -
Aravind Basavapathruni,
Wendy W. Yeh,
Rory Coffey,
James B. Whitney,
Peter Hraber,
Ayush Giri,
Bette T. Korber,
Srinivas S. Rao,
Gary J. Nabel,
John R. Mascola,
Michael S. Seaman,
Norman L. Letvin
Publication year - 2010
Publication title -
journal of virology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.617
H-Index - 292
eISSN - 1070-6321
pISSN - 0022-538X
DOI - 10.1128/jvi.01679-09
Subject(s) - virology , simian immunodeficiency virus , biology , virus , neutralizing antibody , vaccination , viral envelope , antibody , viral evolution , mutation , neutralization , genetics , gene , genome
The evolution of envelope mutations by replicating primate immunodeficiency viruses allows these viruses to escape from the immune pressure mediated by neutralizing antibodies. Vaccine-induced anti-envelope antibody responses may accelerate and/or alter the specificity of the antibodies, thus shaping the evolution of envelope mutations in the replicating virus. To explore this possibility, we studied the neutralizing antibody response and the envelope sequences in rhesus monkeys vaccinated with eithergag -pol -nef immunogens orgag -pol -nef immunogens in combination withenv and then infected with simian immunodeficiency virus (SIV). Using a pseudovirion neutralization assay, we demonstrate that envelope vaccination primed for an accelerated neutralizing antibody response following virus challenge. To monitor viral envelope evolution in these two cohorts of monkeys, full-length envelopes from plasma virus isolated at weeks 37 and 62 postchallenge were sequenced by single genome amplification to identify sites of envelope mutations. We show thatenv vaccination was associated with a change in the pattern of envelope mutations. Prevalent mutations in sequences fromgag -pol -nef vaccinees included deletions in both variable regions 1 and 4 (V1 and V4), whereas deletions in theenv vaccinees occurred only in V1. These data show thatenv vaccination altered the focus of the antibody-mediated selection pressure on the evolution of envelope following SIV challenge.