HPV innate immunity

Abstract

{HPV} infections of the epidermis and anogenital tract occur frequently in healthy individuals, and 'high risk' {HPV} types are a major risk factor for cervical cancer. The first line of defense against {HPV} is the innate immune system, which provides non specific protection against a variety of pathogens and also enhances the adaptive immune response. However, {HPV}-infected cells often evade innate immune recognition and elimination. {HPV} gene expression and release of virus occur in superficial squamous cells where virus antigens are not readily detected, and keratinocytes are not lysed during {HPV} infection so there is no inflammatory response. In addition, {HPV} early proteins inhibit specific components of the innate immune system. E6 and E7 inhibit signaling by type I interferons and decrease expression of multiple interferon-inducible genes. E5 and E7 inhibit expression of major histocompatibility complex class I proteins on the cell surface. {HPV}-infected cells are resistant to lysis by natural killer ({NK}) cells, but are sensitive to cytokine-activated {NK} cells. Activated macrophages also kill {HPV}-infected cells and control malignant development. Thus, innate immunity is important for prevention of {HPV} infections, but {HPV} often persists due to evasion or inactivation of innate defenses.