Rhadinovirus Host Entry by Co-operative Infection

PLoS Pathogens

Janet S. May¹  Ricardo Milho¹  Philip G. Stevenson²  Clara Lawler² 

[1] Division of Virology, Department of Pathology, University of Cambridge, Cambridge, United Kingdom;Sir Albert Sakzewski Virus Research Centre, School of Chemistry and Molecular Biosciences, Royal Children’s Hospital and University of Queensland, Brisbane, Australia

关键词: Virions;    Alveolar macrophages;    Macrophages;    DAPI staining;    Cell binding;    Epithelial cells;    B cells;    Antibodies;   

DOI  :  10.1371/journal.ppat.1004761

学科分类：生物科学（综合）

来源: Public Library of Science

【 摘 要 】

Rhadinoviruses establish chronic infections of clinical and economic importance. Several show respiratory transmission and cause lung pathologies. We used Murid Herpesvirus-4 (MuHV-4) to understand how rhadinovirus lung infection might work. A primary epithelial or B cell infection often is assumed. MuHV-4 targeted instead alveolar macrophages, and their depletion reduced markedly host entry. While host entry was efficient, alveolar macrophages lacked heparan - an important rhadinovirus binding target - and were infected poorly ex vivo. In situ analysis revealed that virions bound initially not to macrophages but to heparan+ type 1 alveolar epithelial cells (AECs). Although epithelial cell lines endocytose MuHV-4 readily in vitro, AECs did not. Rather bound virions were acquired by macrophages; epithelial infection occurred only later. Thus, host entry was co-operative - virion binding to epithelial cells licensed macrophage infection, and this in turn licensed AEC infection. An antibody block of epithelial cell binding failed to block host entry: opsonization provided merely another route to macrophages. By contrast an antibody block of membrane fusion was effective. Therefore co-operative infection extended viral tropism beyond the normal paradigm of a target cell infected readily in vitro; and macrophage involvement in host entry required neutralization to act down-stream of cell binding.

【 授权许可】

CC BY