부산대학교 도서관

Virus entry into host cells is a complex process that is largely regulated by the access to specific cellular receptors. Human adenoviruses (HAdVs) and many other viruses use cell adhesion molecules such as the Coxsackievirus and adenovirus receptor (CAR) for attachment to and entry into target cells. These molecules are rarely expressed on the apical side of polarized epithelial cells, which raise the question how adenovirus - and other viruses that engage cell adhesion molecules - enter polarized cells from the apical side to initiate infection. We have previously shown that species C HAdVs utilize lactoferrin - a common innate immune component secreted to respiratory mucosa for infection via unknown mechanisms. Using a series of biochemical, cellular, and molecular biology approaches, we map this effect to the proteolytically cleavable, positively charged, N-terminal 49 residues of human lactoferrin (hLF) known as lactoferricin (hLfcin). Lfcin binds to the hexon protein on the viral capsid, and anchors the virus to an unknown receptor of target cells, resulting in infection. These findings suggests that HAdVs use distinct cell entry mechanisms at different stages of infection. To initiate infection, entry is likely to occur at the apical side of polarized epithelial cells largely by means of hLF and hLfcin bridging HAdV capsids via hexons to as yet unknown receptors, and when infection is established, progeny virions released from the basolateral side enter neighbouring cells by means of hLF/hLfcin and CAR in parallel. [ABSTRACT FROM AUTHOR]