title: Host cell autophagy modulates early stages of adenovirus infections in airway epithelial cells.
abstract: Human adenoviruses typically cause mild infections in the upper or lower respiratory tract, gastrointestinal tract, or ocular epithelium. However, adenoviruses may be life-threatening in patients with impaired immunity and some serotypes cause epidemic outbreaks. Attachment to host cell receptors activates cell signaling and virus uptake by endocytosis. At present, it is unclear how vital cellular homeostatic mechanisms affect these early steps in the adenovirus life cycle. Autophagy is a lysosomal degradation pathway for recycling intracellular components that is upregulated during periods of cell stress. Autophagic cargo is sequestered in double-membrane structures called autophagosomes that fuse with endosomes to form amphisomes which then deliver their content to lysosomes. Autophagy is an important adaptive response in airway epithelial cells targeted by many common adenovirus serotypes. Using two established tissue culture models, we demonstrate here that adaptive autophagy enhances expression of the early region 1 adenovirus protein, induction of mitogen-activated protein kinase signaling, and production of new viral progeny in airway epithelial cells infected with adenovirus type 2. We have also discovered that adenovirus infections are tightly regulated by endosome maturation, a process characterized by abrupt exchange of Rab5 and Rab7 GTPases, associated with early and late endosomes, respectively. Moreover, endosome maturation appears to control a pool of early endosomes capable of fusing with autophagosomes which enhance adenovirus infection. Many viruses have evolved mechanisms to induce autophagy in order to aid their own replication. Our studies reveal a novel role for host cell autophagy that could have a significant impact on the outcome of respiratory infections.
authors.affiliation: Department of Molecular Biology and Microbiology, Case Western Reserve University, Cleveland, Ohio, USA.
authors.forename: Xuehuo
authors.initials: X
authors.lastname: Zeng
authors.forename: Cathleen R
authors.initials: CR
authors.lastname: Carlin
mesh_terms: D000258:Adenovirus Infections, Human / Q000821:virology*; D000260:Adenoviruses, Human / Q000472:pathogenicity*; D001343:Autophagy; D002460:Cell Line; D011992:Endosomes / Q000378:metabolism; D004847:Epithelial Cells / Q000502:physiology* / Q000821:virology*; D006801:Humans; D015398:Signal Transduction; D014779:Virus Replication