Transmission of Rhinovirus infection highly influenced by immune system related genetic polymorphisms

Rhinovirus are picornavirus with over 150 serotypes and 3 species. Although usually causing common colds, in Asthma, COPD and elders it may cause life-threatening disease. Both environmental and genetic susceptibility factors may play a role in rhinovirus epidemiology. In the present study we evaluated the influence of immune-system related genetic variations (TOLLIP rs5743899, IL6 rs1800795, IL1B rs16944, TNFA rs1800629) in the modulation of rhinovirus infection susceptibility. Blood samples and monthly nasal swabs were collected from 89 volunteers. DNA and RNA were purified with Qiagen column based kits. Viral RNA was quantified by RT- qPCR on Light cycler 1.1 (Roche). Polymorphisms were genotyped by PCR-RFLP. TOLLIP and IL6 polymorphisms (but not IL1B and TNF) were found to influence rhinovirus nasal detection. TOLLIP-G individuals were more often year-long rhinovirus free (p<0.028). This fully agrees with molecular mechanisms as free Rhinovirus particles, are detected by TLR2 which is inhibited by TOLLIP. TOLLIP-G decreases TOLLIP expression, increasing TLR2 and protecting from Rhinovirus infection. TOLLIP G also sustains production of IL6 needed for viral clearance post-infection. However, in the absence of the TOLLIP G allele, and of the IL6-C allele there is low IL6 production leading to a poorer Immune response and higher viral titres.