Dynamics of viral evolution and neutralizing antibody response after HIV-1 superinfection.
Investigating the incidence and prevalence of HIV-1 superinfection is challenging due to the complex dynamics of two infecting strains. The superinfecting strain can replace the initial strain, be transiently expressed, or persist along with the initial strain in distinct or in recombined forms. Various selective pressures influence these alternative scenarios in different HIV-1 coding regions. We hypothesized that the potency of the neutralizing antibody (NAb) response to autologous viruses would modulate viral dynamics in env following superinfection in a limited set of superinfection cases. HIV-1 env pyrosequencing data were generated from blood plasma collected from 7 individuals with evidence of superinfection. Viral variants within each patient were screened for recombination, and viral dynamics were evaluated using nucleotide diversity. NAb responses to autologous viruses were evaluated before and after superinfection. In 4 individuals, the superinfecting strain replaced the original strain. In 2 individuals, both initial and superinfecting strains continued to cocirculate. In the final individual, the surviving lineage was the product of interstrain recombination. NAb responses to autologous viruses that were detected within the first 2 years of HIV-1 infection were weak or absent for 6 of the 7 recently infected individuals at the time of and shortly following superinfection. These 6 individuals had detectable on-going viral replication of distinct superinfecting virus in the env coding region. In the remaining case, there was an early and strong autologous NAb response, which was associated with extensive recombination in env between initial and superinfecting strains. This extensive recombination made superinfection more difficult to identify and may explain why the detection of superinfection has typically been associated with low autologous NAb titers.
University of California, San Diego, La Jolla, California, USA.
Antoine
A
Chaillon
Gabriel A
GA
Wagner
N Lance
NL
Hepler
Susan J
SJ
Little
Sergei L
SL
Kosakovsky Pond
Gemma
G
Caballero
Mary E
ME
Pacold
Pham
P
Phung
Terri
T
Wrin
Douglas D
DD
Richman
Joel O
JO
Wertheim
Davey M
DM
Smith
D000328:Adult; D057134:Antibodies, Neutralizing / Q000276:immunology*; D005075:Biological Evolution; D015483:HIV Antibodies / Q000276:immunology; D015658:HIV Infections / Q000276:immunology / Q000821:virology*; D015497:HIV-1 / Q000145:classification / Q000235:genetics* / Q000302:isolation & purification / Q000502:physiology; D006801:Humans; D008297:Male; D008875:Middle Aged; D008969:Molecular Sequence Data; D010802:Phylogeny; D011995:Recombination, Genetic; D015163:Superinfection / Q000276:immunology / Q000821:virology*; D055815:Young Adult; D054299:env Gene Products, Human Immunodeficiency Virus / Q000235:genetics
D057134:Antibodies, Neutralizing; D015483:HIV Antibodies; D054299:env Gene Products, Human Immunodeficiency Virus