Viral phenotypes and antibody responses in long-term survivors infected with attenuated human immunodeficiency virus type 1 containing deletions in the nef and long terminal repeat regions.
The Sydney Blood Bank Cohort (SBBC) consists of eight blood transfusion recipients infected with nef-attenuated human immunodeficiency virus type 1 (HIV-1) acquired from a single donor. Here, we show that viral phenotypes and antibody responses differ considerably between individual cohort members, despite the single source of infection. Replication of isolated virus varied from barely detectable to similar to that of the wild-type virus, and virus isolated from five SBBC members showed coreceptor usage signatures unique to each individual. Higher viral loads and stronger neutralizing antibody responses were associated with better-replicating viral strains, and detectable viral replication was essential for the development of strong and sustained humoral immune responses. Despite the presence of strong neutralizing antibodies in a number of SBBC members, disease progression was not prevented, and each cohort member studied displayed a unique outcome of infection with nef-attenuated HIV-1.
Verity
Erin E
EE
Department of Microbiology, Monash University, Clayton, Victoria, Australia.
Zotos
Dimitra
D
Wilson
Kim
K
Chatfield
Catherine
C
Lawson
Victoria A
VA
Dwyer
Dominic E
DE
Cunningham
Anthony
A
Learmont
Jennifer
J
Dyer
Wayne
W
Sullivan
John
J
Churchill
Melissa
M
Wesselingh
Steven L
SL
Gabuzda
Dana
D
Gorry
Paul R
PR
McPhee
Dale A
DA
D000914:Antibodies, Viral / Q000097:blood*; D001803:Blood Transfusion; D018791:CD4 Lymphocyte Count; D015331:Cohort Studies; D018450:Disease Progression; D015693:Gene Products, nef / Q000235:genetics*; D015483:HIV Antibodies / Q000097:blood*; D015658:HIV Infections / Q000276:immunology / Q000821:virology*; D016325:HIV Long Terminal Repeat / Q000235:genetics*; D020276:HIV Long-Term Survivors; D015497:HIV-1 / Q000235:genetics* / Q000276:immunology / Q000302:isolation & purification / Q000502:physiology; D006801:Humans; D007074:Immunoglobulin G / Q000097:blood; D009500:Neutralization Tests; D010641:Phenotype; D017384:Sequence Deletion; D019562:Viral Load; D014779:Virus Replication; D054311:nef Gene Products, Human Immunodeficiency Virus
D000914:Antibodies, Viral; D015693:Gene Products, nef; D015483:HIV Antibodies; D007074:Immunoglobulin G; D054311:nef Gene Products, Human Immunodeficiency Virus; C514837:nef protein, Human immunodeficiency virus 1