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Background Dengue is a systemic viral infection that spreads to humans by the bite of infected Aedes mosquitoes. The secreted NS1 protein of dengue virus activates macrophages and human PBMCs via TLR4 and induce the release of pro-inflammatory cytokines which is responsible for the pathogenesis of disease. Mutations in TLR4 gene have been associated with the increased susceptibility to many viral, bacterial and parasitic diseases. Objective To study the impact of TLR4 Asp299Gly (rs4986790) and Thr399Ile (rs4986791) gene polymorphisms with susceptibility to dengue infection. Methods A total of 120 dengue infected (57; DHF/DSS and 63; DF) and 200 healthy controls were included in the study. TLR4 Asp299Gly and Thr399Ile gene polymorphisms was studied by PCR-RFLP. Expression of TLR4 mRNA was evaluated by rRT-PCR. Results Individuals with heterozygous genotype for TLR4 Asp299Gly and Thr399Ile polymorphisms had increased susceptibility to dengue infection (OR-1.70, 95% CI = 1.01–2.86 P = 0.042 and OR-2.17, 95% CI = 1.10–4.28, P = 0.024, respectively). The frequency of Gly and Ile alleles were higher in dengue patients as compared to controls (OR-1.67, 95% CI = 1.05–2.64, P = 0.029 and OR-2.20, 95% CI = 1.19–4.07, P = 0.011, respectively). IIe/Gly haplotype was associated with the risk of the disease when compared with controls (OR = 3.15, 95% CI = 1.09–9.09, P = 0.035). The mRNA expression was higher in DF when compared with DHF/DSS and controls ( P = 0.040 and 0.009, respectively). Conclusion A higher expression of TLR4 mRNA was associated with DF. The TLR4 Asp299Gly and Thr399Ile gene polymorphisms were associated with the susceptibility of dengue infection probably by altering the immune response. [ABSTRACT FROM AUTHOR]

Dengue infection is caused by flavivirus is one of the leading cause of mortality. There are certain factors which play role in the transformation of a mild form of the disease (DF) into a severe form (DHF) but the most important ones are: viral strain virulence, host genetics, and host immune status. In severe dengue infection, plasma leakage occurs due to vascular endothelial cell activation through expression of adhesion molecule like intercellular cell adhesion molecule-1 (ICAM-1). A total of 100 dengue patients (DF; n = 53 and DHF/DSS; n = 47) and 200 healthy controls were included in the study. ICAM-1 K469E genotyping was done by polymerase chain reaction-restriction fragment length polymorphism (PCR- RFLP). Expression of ICAM-1 mRNA was done by Real time reverse transcription- PCR (rRT-PCR). Patients with homozygous genotype (EE) have 3.22 fold risk (P = 0.008) of developing severe form of disease (DHF/DSS) as compared to other genotypes. Patients with DHF/DSS exhibit higher expression of ICAM-1 mRNA as compared to dengue fever and controls (P = 0.001 and < 0.001). Patients (DHF/DSS) with homozygous (EE) genotype exhibit higher expression of ICAM-1 mRNA when compared with wild type (KK) genotype (P = 0.005). This study suggests a possible association between the ICAM-1 polymorphism and the disease severity. [ABSTRACT FROM AUTHOR]

A multitude of host genetic factors plays a crucial role in susceptibility to HIV-1 infection and progression to AIDS, which is highly variable among individuals and populations. This review focuses on the chemokine-receptor and chemokine genes, which were extensively studied because of their role as HIV co-receptor or co-receptor competitor and influences the susceptibility to HIV-1 infection and progression to AIDS in HIV-1 infected individuals. [ABSTRACT FROM AUTHOR]