Immune responses underpinning acute co-infections with unrelated viruses: timing and location matter.

Immunity to viral infections is generally studied in isolation by measuring immune responses towards a single virus. However, concurrent or sequential viral co-infections can occur in a single host. Viral co-infections can impact anti-viral immunity by altering protective responses and driving immunopathology. Understanding immune mechanisms towards co-infections with unrelated viruses is highly relevant to treatment and prevention. There is, however, a paucity of data on immune responses towards viral co-infections, especially with unrelated viruses. Most commonly studied viral co-infections include chronic viruses, such as hepatitis B, hepatitis C, and human immunodeficiency virus, as well as viruses infecting the same tissues, including respiratory viral co-infections. However, the immunological consequences of co-infections with unrelated acute viruses are less understood, especially for viruses affecting different anatomical sites. As co-infecting viruses can have a more pronounced impact on human health compared to infection with a single virus, understanding immune responses and, especially, the impact of timing, sequence, and location of viral co-infections is of key importance. This review provides an overview of the current knowledge on acute viral co-infections with unrelated viruses, underpinning immune mechanisms, and implications for vaccination regimens.