title: 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.
abstract: 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.
authors.affiliation: Department of Microbiology, Monash University, Clayton, Victoria, Australia.
authors.forename: Erin E
authors.initials: EE
authors.lastname: Verity
authors.forename: Dimitra
authors.initials: D
authors.lastname: Zotos
authors.forename: Kim
authors.initials: K
authors.lastname: Wilson
authors.forename: Catherine
authors.initials: C
authors.lastname: Chatfield
authors.forename: Victoria A
authors.initials: VA
authors.lastname: Lawson
authors.forename: Dominic E
authors.initials: DE
authors.lastname: Dwyer
authors.forename: Anthony
authors.initials: A
authors.lastname: Cunningham
authors.forename: Jennifer
authors.initials: J
authors.lastname: Learmont
authors.forename: Wayne
authors.initials: W
authors.lastname: Dyer
authors.forename: John
authors.initials: J
authors.lastname: Sullivan
authors.forename: Melissa
authors.initials: M
authors.lastname: Churchill
authors.forename: Steven L
authors.initials: SL
authors.lastname: Wesselingh
authors.forename: Dana
authors.initials: D
authors.lastname: Gabuzda
authors.forename: Paul R
authors.initials: PR
authors.lastname: Gorry
authors.forename: Dale A
authors.initials: DA
authors.lastname: McPhee
mesh_terms: 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
chemical_list: 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