Characterization of a U L 49-Null Mutant: VP22 of Herpes Simplex Virus Type 1 Facilitates Viral Spread in Cultured Cells and the Mouse Cornea

• Published in: Journal of virology 2006-09, Vol.80 (17), p.8664-8675
• Main Authors: Duffy, Carol, LaVail, Jennifer H., Tauscher, Andrew N., Wills, Elizabeth G., Blaho, John A., Baines, Joel D.
• Format: Article
• Language: English
• ISSN: 0022-538X; 1098-5514
• DOI: 10.1128/JVI.00498-06

Herpes simplex virus type 1 (HSV-1) virions, like those of all herpesviruses, contain a proteinaceous layer termed the tegument that lies between the nucleocapsid and viral envelope. The HSV-1 tegument is composed of at least 20 different viral proteins of various stoichiometries. VP22, the product of the U L 49 gene, is one of the most abundant tegument proteins and is conserved among the alphaherpesviruses. Although a number of interesting biological properties have been attributed to VP22, its role in HSV-1 infection is not well understood. In the present study we have generated both a U L 49-null virus and its genetic repair and characterized their growth in both cultured cells and the mouse cornea. While single-step growth analyses indicated that VP22 is dispensable for virus replication at high multiplicities of infection (MOIs), analyses of plaque morphology and intra- and extracellular multistep growth identified a role for VP22 in viral spread during HSV-1 infection at low MOIs. Specifically, VP22 was not required for either virion infectivity or cell-cell spread but was required for accumulation of extracellular virus to wild-type levels. We found that the absence of VP22 also affected virion composition. Intracellular virions generated by the U L 49-null virus contained reduced amounts of ICP0 and glycoproteins E and D compared to those generated by the wild-type and U L 49-repaired viruses. In addition, viral spread in the mouse cornea was significantly reduced upon infection with the U L 49-null virus compared to infection with the wild-type and U L 49-repaired viruses, identifying a role for VP22 in viral spread in vivo as well as in vitro.