Human genetic determinants of dengue virus susceptibility.
Dengue virus (DENV) is an emerging mosquito-borne pathogen that produces significant morbidity worldwide resulting in an estimated 50-100 million infections annually. DENV causes a spectrum of illness ranging from inapparent infection to life-threatening hemorrhagic fever and shock. The varied DENV disease outcome is determined by complex interactions between immunopathologic, viral, and human genetic factors. This review summarizes these interactions with a focus on human genetic determinants of DENV susceptibility, including human leukocyte antigens, blood type, and single nucleotide polymorphisms in immune response genes that have been associated with DENV disease. We also discuss other factors related to DENV outcome including viral genetic determinants, age, ethnicity, and nutritional status as they relate to DENV susceptibility. We emphasize the need for functional genetics studies to complement association-based data and we call for controlled study designs and standard clinical DENV disease definitions that will strengthen conclusions based on human genetic DENV studies.
Coffey
Lark L
LL
Unité des Interactions Moléculaires Flavivirus-Hôtes, Institut Pasteur, 75724 Paris, France. lark.coffey@pasteur.fr
Mertens
Eva
E
Brehin
Anne-Claire
AC
Fernandez-Garcia
Maria Dolores
MD
Amara
Ali
A
Després
Philippe
P
Sakuntabhai
Anavaj
A
D003715:Dengue / Q000235:genetics*; D003716:Dengue Virus / Q000472:pathogenicity*; D004198:Disease Susceptibility; D006790:Host-Parasite Interactions; D006801:Humans