Multiple transmissions of a stable human leucocyte antigen-B27 cytotoxic T-cell-escape strain of HIV-1 in The Netherlands.
OBJECTIVE
The evolution of HIV-1 is largely shaped by the cytotoxic T-cell (CTL) response of the host as encoded by the human leucocyte antigen (HLA) genes. Certain HLA-B alleles can delay disease progression, but it is uncertain whether this protection will sustain or whether the virus is in the process of adaptation. In The Netherlands, HLA-B27 is moderately prevalent (approximately 8-16% of HLA-B alleles). If adaptation to HLA-B alleles is in progress, virus strains carrying escape mutations to HLA-B27 should appear in the epidemic by now.


METHODS
A subtype B HIV-1 strain carrying a HLA-B27 CTL-escape mutation in the main Gag-p24 KK10 epitope, R264G, together with a compensatory mutation outside this epitope, E260D, was detected in four patients from Amsterdam, The Netherlands, by sequence analysis of the gag gene. The patients were a drug user and three men who have sex with men, and were infected with HIV-1 between 2002 and 2008.


METHODS
Characterization and evolutionary analysis of the HIV-1 CTL-escape strain was done by sequence analysis of serial blood plasma samples.


RESULTS
The mutations involved were stable during follow-up and after transmission, also in two individuals lacking HLA-B27.


CONCLUSIONS
The finding that a stable HLA-B27 CTL-escape strain is circulating in The Netherlands has important implications for the understanding of virus-host interactions and vaccine design alike. Vaccines targeted at inducing a CTL response might easily be circumvented by the virus. Also, patients carrying protective HLA alleles might not be protected anymore from disease progression in the future.
Cornelissen
Marion
M
Laboratory of Experimental Virology, Center for Infection and Immunity Amsterdam, The Netherlands.
Hoogland
Frederik M
FM
Back
Nicole K T
NK
Jurriaans
Suzanne
S
Zorgdrager
Fokla
F
Bakker
Margreet
M
Brinkman
Kees
K
Prins
Maria
M
van der Kuyl
Antoinette C
AC
D000328:Adult; D005838:Genotype; D016655:HIV Core Protein p24 / Q000235:genetics / Q000276:immunology; D015658:HIV Infections / Q000276:immunology / Q000635:transmission / Q000821:virology*; D015497:HIV-1 / Q000145:classification / Q000235:genetics*; D015796:HLA-B27 Antigen / Q000235:genetics / Q000276:immunology*; D018451:Homosexuality, Male; D006801:Humans; D007108:Immune Tolerance; D008297:Male; D008875:Middle Aged; D009154:Mutation; D012367:RNA, Viral / Q000235:genetics; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology*
D016655:HIV Core Protein p24; D015796:HLA-B27 Antigen; D012367:RNA, Viral