Can the common cold protect you from influenza? A murine model of respiratory viral co-infection.

Abstract

Abstract Clinical cases demonstrate that up to 30% of respiratory infections involve more than one virus with rhinovirus being one of the most common in co-infections. Interestingly, rhinovirus has been found to exacerbate disease when co-infecting with adenovirus, whereas it can modulate disease when co-infecting with influenza A virus. However, there has yet to be a clear connection for how these viruses interact in the host to alter immune responses and disease severity. We are using a murine model of respiratory viral co-infection to determine how minor group rhinovirus (RV1B) affects pathogenesis during influenza A virus (PR8) infection. BALB/c mice were infected with RV1B or mock-infected two days before infecting with a high (100% lethal) or low (40% lethal) dose of PR8. Mice co-infected with RV1B and low dose PR8 had reduced clinical signs, weight loss and mortality compared to mice infected with PR8 alone. However, RV1B did not reduce disease severity upon infection with a high dose of PR8. Groups of mice were infected with RV1B or mock-infected two days prior to infection with low dose PR8 and were sacrificed 4 and 7 days later to quantify PR8 in the lungs. Single- and co-infected mice had similar PR8 titers on day 4; however, the co-infected group completely cleared PR8 on day 7 while the single infected group still had detectable titers. These results suggest that rhinovirus stimulates an immune response that promotes viral clearance and recovery upon infection with influenza A virus. Ongoing work will characterize this response to explain how respiratory viral co-infections can manipulate host immune responses to change disease outcome.