Polymorphisms in Human Leukocyte Antigens, Human Platelet Antigens, and Cytokine Genes in Hantavirus Cardiopulmonary Syndrome Patients from Ribeirao Preto, Brazil

Hantavirus cardiopulmonary syndrome is a severe human disease associated with hantavirus infection. The clinical course of illness varies greatly among individuals, possibly due to viral and immunological elements and the influence of host genetic factors on clinical outcome. As the magnitude of immune activation has been associated with disease severity, polymorphisms in genes involved in the immune response that may affect the development of this syndrome were investigated. Polymorphisms in the TGF-, IL-10, IL-6, and IFN- genes, human leukocyte antigens (HLA), and human platelet alloantigens (HPA) genes were investigated in 122 patients with Araraquara virus infection from RibeirAo Preto, Brazil. Patients were divided into two groups: hantavirus cardiopulmonary syndrome (HCPS group; n=26) and hantavirus seropositive only (n=96). The frequencies of HLA alleles, cytokines and platelet antigen genotypes were evaluated in both groups and compared to a control group. The data demonstrated no significant influence of the HLA alleles, HPA, IL-6, and IL-10 genotypes on susceptibility to hantavirus infection. However, the hantavirus seropositive group presented a significantly higher frequency of a polymorphism associated with a high IFN- production than the HCPS group. In addition, a genotype associated with high TGF- production was found more frequently in individuals infected with hantavirus than in the control group. This phenotype was associated with a less intense thrombocytopenia in the HCPS group and may be protective against the most severe form of hantavirus disease. More studies are required to quantify further the influence of the high TGF- producer phenotype on the outcome of hantavirus infection. J. Med. Virol. 86:1962-1970, 2014. (c) 2013 Wiley Periodicals, Inc.