RESUMEN
Chikungunya virus (CHIKV) is an alphavirus from the Togaviridae family that causes acute arthropathy in humans. It is an arthropod-borne virus transmitted initially by the Aedes (Ae) aegypti and after 2006's epidemic in La Reunion by Ae albopictus due to an adaptive mutation of alanine for valine in the position 226 of the E1 glycoprotein genome (A226V). The first isolated cases of CHIKV were reported in Tanzania, however since its arrival to the Western Hemisphere in 2013, the infection became a pandemic. After a mosquito bite from an infected viremic patient the virus replicates eliciting viremia, fever, rash, myalgia, arthralgia, and arthritis. After the acute phase, CHIKV infection can progress to a chronic stage where rheumatic symptoms can last for several months to years. Although there is a great number of studies on the pathogenesis of CHIKV infection not only in humans but also in animal models, there still gaps in the proper understanding of the disease. To this date, it is unknown why a percentage of patients do not develop clinical symptoms despite having been exposed to the virus and developing an adaptive immune response. Also, controversy stills exist on the pathogenesis of chronic joint symptoms. It is known that host immune response to an infectious disease is reflected on patient's symptoms. At the same time, it is now well-established that host genetic variation is an important component of the varied onset, severity, and outcome of infectious disease. It is essential to understand the interaction between the aetiological agent and the host to know the chronic sequelae of the disease. The present review summarizes the current findings on human host genetics and its relationship with immune response in CHIKV infection.
RESUMEN
Host immune response and virulence factors are key to disease susceptibility. However, there are no known association studies of human leukocyte antigen (HLA) class I and II alleles with chikungunya virus (CHIKV) infection in the Latin American population. Here, we aimed to identify HLA alleles present in patients with CHIKV infection versus healthy controls as well as the allelic association with the clinical spectrum of the disease. We conducted a cross-sectional analysis of a community cohort and included patients aged 18 years and older with serologically confirmed CHIKV infection. HLA typing of HLA-A, HLA-B, and HLA-DRB1 alleles was performed. Two-by-two tables were used to establish associations between allele presence and clinical characteristics. Data from 65 patients with confirmed CHIKV infection were analyzed for HLA typing. CHIKV infection was significantly associated with the presence of HLA-A*68 [p = .005; odds ratio (OR): 8.90; 95% confidence interval (CI): 1.88-42.13], HLA-B*35 (p = .03; OR: 2.01; 95% CI: 1.06-3.86), HLA-DRB*01 (p <.001; OR: 5.70; 95% CI: 1.95-16.59), HLA-DRB1*04 (p <.001; OR: 7.37; 95% CI: 3.33-16.30), and HLA-DRB1*13 (p = .004; OR: 3.75; 95% CI: 1.50-9.39) alleles in patients versus healthy subjects. A statistically significant relationship was found between the presence of a rash on the face or abdomen and the presence of HLA-DRB1*04 (p = .028; OR: 3.2; 95% CI: 1.11-9.15 and p = .007; OR: 4.33; 95% CI: 1.45-12.88, respectively). Our study demonstrated that, in our cohort, HLA type I and type II alleles are associated with CHIKV infection, and an HLA type II allele is associated with dermatological symptoms. Further research is needed to establish a path for future investigation of genes outside the HLA system to improve knowledge of the pathophysiology of CHIKV infection and its host-pathogen interaction.