HIV-1 evolution following transmission to an HLA-B*5801-positive patient.
The human immunodeficiency virus type 1 (HIV-1)-specific immune responses of patients with the HLA-B*57/5801 alleles who spontaneously control viral replication serve as an important model for T cell-based HIV-1 vaccines. Determining the breadth of this response and the extent of virologic escape in primary infection in these patients is therefore critical. Here we document the development of mutations in 3 HLA-B*5801-restricted epitopes in gag, nef, and pol in an HLA-B*5801-positive patient who had a viral load of only 1159 copies/mL at day 167 after infection. A full genome sequence analysis was performed to determine the extent of mutations in HLA-B*5801-restricted epitopes, and longitudinal sequence data of specific genes were combined with enzyme-linked immunospot assay analysis of critical epitopes to determine the importance of escape mutations. Thus, relative control of viral replication can be maintained in spite of the rapid development of multiple escape mutations within cytotoxic T lymphocyte epitopes.
O'Connell
Karen A
KA
Department of Medicine, School of Medicine, Bloomberg School of Public Health, Johns Hopkins University, Baltimore, Maryland 21205, USA.
Xu
Jie
J
Durbin
Anna P
AP
Apuzzo
Linda G
LG
Imteyaz
Hejab
H
Williams
Thomas M
TM
Ray
Stuart C
SC
Margolick
Joseph B
JB
Siliciano
Robert F
RF
Blankson
Joel N
JN
D000328:Adult; D000939:Epitopes / Q000235:genetics; D019143:Evolution, Molecular; D005260:Female; D016679:Genome, Viral; D015483:HIV Antibodies / Q000276:immunology; D015658:HIV Infections / Q000276:immunology* / Q000635:transmission / Q000821:virology*; D015497:HIV-1 / Q000145:classification* / Q000235:genetics / Q000276:immunology* / Q000302:isolation & purification; D015235:HLA-B Antigens / Q000276:immunology*; D006801:Humans; D015151:Immunoblotting; D008137:Longitudinal Studies; D008297:Male; D008875:Middle Aged; D020125:Mutation, Missense; D012367:RNA, Viral / Q000235:genetics; D017422:Sequence Analysis, DNA; D019562:Viral Load; D054301:gag Gene Products, Human Immunodeficiency Virus / Q000235:genetics; D054311:nef Gene Products, Human Immunodeficiency Virus / Q000235:genetics; D054302:pol Gene Products, Human Immunodeficiency Virus / Q000235:genetics
D000939:Epitopes; D015483:HIV Antibodies; D015235:HLA-B Antigens; C500126:HLA-B*58:01 antigen; D012367:RNA, Viral; D054301:gag Gene Products, Human Immunodeficiency Virus; D054311:nef Gene Products, Human Immunodeficiency Virus; C514837:nef protein, Human immunodeficiency virus 1; D054302:pol Gene Products, Human Immunodeficiency Virus