A frequent functional toll-like receptor 7 polymorphism is associated with accelerated HIV-1 disease progression.
OBJECTIVE
Toll-like receptors (TLRs) play an important role in the innate immune response to pathogens. TLR7 recognizes RNA of various viruses including HIV. The objective of this study was to examine the influence of individual genetic variations of TLR7 on the susceptibility to and progression of HIV disease.


METHODS
We genotyped a population of 734 HIV-positive adults and 545 healthy controls for three TLR7 single nucleotide polymorphisms. The frequency of TLR7 genetic variations was assessed and related to HIV disease progression. Furthermore, we analyzed peripheral blood mononuclear cells obtained from healthy individuals differing in their TLR7 genotype and assessed their response to a TLR7-specific ligand ex vivo.


RESULTS
Presence of the most frequent TLR7 polymorphism, TLR7 Gln11Leu, was associated with higher viral loads and accelerated progression to advanced immune suppression in HIV patients. Furthermore, in women this polymorphism may be associated with increased HIV-1 susceptibility as it was found more frequently among patients as compared with controls. Peripheral blood mononuclear cells from polymorphism carriers secreted significantly less IFN-alpha following TLR7 activation, whereas IL-6 production remained unaltered.


CONCLUSIONS
This is the first report of a functional TLR7 variant to be associated with susceptibility to and a more severe clinical course of HIV-1 disease. These results may have implications for the risk assessment of individual patients as well as for HIV-1 therapy and vaccination strategies in the future.
Oh
Djin-Ye
DY
Institute for Microbiology and Hygiene, Charité University Medical Center, Berlin, Germany.
Baumann
Konstantin
K
Hamouda
Osamah
O
Eckert
Jana K
JK
Neumann
Konrad
K
Kücherer
Claudia
C
Bartmeyer
Barbara
B
Poggensee
Gabriele
G
Oh
Nari
N
Pruss
Axel
A
Jessen
Heiko
H
Schumann
Ralf R
RR
D000328:Adult; D018791:CD4 Lymphocyte Count; D002478:Cells, Cultured; D015331:Cohort Studies; D018450:Disease Progression; D005260:Female; D020022:Genetic Predisposition to Disease; D005838:Genotype; D015658:HIV Infections / Q000235:genetics* / Q000276:immunology / Q000821:virology; D015497:HIV-1 / Q000302:isolation & purification*; D006801:Humans; D007113:Immunity, Innate / Q000235:genetics; D008297:Male; D020641:Polymorphism, Single Nucleotide; D051199:Toll-Like Receptor 7 / Q000235:genetics* / Q000276:immunology; D019562:Viral Load
C495348:TLR7 protein, human; D051199:Toll-Like Receptor 7