A herpes simplex virus 1 recombinant lacking the glycoprotein G coding sequences is defective in entry through apical surfaces of polarized epithelial cells in culture and in vivo
Lc. Tran et al., A herpes simplex virus 1 recombinant lacking the glycoprotein G coding sequences is defective in entry through apical surfaces of polarized epithelial cells in culture and in vivo, P NAS US, 97(4), 2000, pp. 1818-1822
Citations number
20
Categorie Soggetti
Multidisciplinary
Journal title
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
During infection of a new host, the first surfaces encountered by herpes si
mplex viruses are the apical membranes of epithelial cells of mucosal surfa
ces, These cells are highly polarized, and the protein composition of their
apical and basolateral membranes are very different, so that different vir
al entry pathways have evolved for each surface. To determine whether the v
iral glycoprotein G (gG) is specifically required for efficient infection o
f a particular surface of polarized cells, apical and basal surfaces were i
nfected with wild-type virus or a gG deletion mutant. After infection of po
larized cells in culture, the gG(-) virus was deficient in infection of api
cal surfaces but was able to infect cells through basal membranes, replicat
e, and spread into surrounding cells. The gG-dependent step in apical infec
tion was a stage beyond attachment. After in vivo infection of apical surfa
ces of epithelial cells of nonscarified mouse corneas, infection by glycopr
otein C- or gG(-) virus was considerably reduced as compared with that obse
rved after infection with wild-type virus. In contrast, when corneas were s
carified, allowing virus access to other cell surfaces, the gG and glycopro
tein C deletion mutants infected eyes as efficiently as wild-type viruses.
A secondary mutation allowing infection of apical surfaces by gG(-) virus a
rose readily during passage of the virus in nonpolarized cells, indicating
that either the gG-dependent step of apical infection can be bypassed or th
at another viral protein can acquire the same function.