The domains of glycoprotein D required to block apoptosis depend on whether glycoprotein D is present in the virions carrying herpes simplex virus 1 genome lacking the gene encoding the glycoprotein
Gy. Zhou et B. Roizman, The domains of glycoprotein D required to block apoptosis depend on whether glycoprotein D is present in the virions carrying herpes simplex virus 1 genome lacking the gene encoding the glycoprotein, J VIROLOGY, 75(13), 2001, pp. 6166-6172
An earlier report showed that viruses lacking the open reading frames encod
ing glycoproteins J and D but containing the glycoprotein D in their envelo
pes (gD-/+ stocks) and viruses lacking both the open reading frames and the
glycoproteins in their envelopes (gD-/- stocks) induce apoptosis (G, Zhou,
V, Galvan, G, Campadelli-Fiume, and B, Roizman, J, Virol, 74:11782-11791,
2000), Furthermore, apoptosis was blocked by delivery in trans of genes exp
ressing glycoprotein D or J. Whereas gD-/- stocks attach but cannot initiat
e productive infection, gD-/+ stocks infect cells and produce gD-/- progeny
virus. The difference in the infectivity of these two stocks suggested the
possibility that the requirements for blocking apoptosis mag. be different
. To test this hypothesis, we cloned into baculoviruses the entire wild-typ
e glycoprotein D (Bac-gD-WT), the ectodomain only (Bac-gD-A), the ectodomai
n and the transmembrane domain (Bac-gD-B), the ectodomain and the cytoplasm
ic domain without the transmembrane domain (Bac-gD-C), or the transmembrane
domain and the carboxyl-terminal cytoplasmic domain (Bac-gD-D),We report t
he following, Apoptosis induced by gD-/+ stocks was blocked by delivery in
trans of recombinant baculovirus Bac-gD-WT, Bac-gD-A, Bac-gD-B, or Bac-gD-C
but not of Bac-gD, Apoptosis induced by gD-/- stocks was blocked by Bac-gD
-WT or by a mixture of Bac-gD-B and Bac-gD-D but not by any baculoviruses e
xpressing truncated glycoprotein D alone or by the mixture of Bac-gD-A and
Bac-gD-D, We conclude that the requirements to block apoptosis induced by t
he two virus stocks are different. The go ectodomain is sufficient to block
apoptosis induced by go, whereas both the ectodomain and the cytoplasmic d
omain are required to black apoptosis induced by gD-/-stocks. The results i
ndicate that in the case of gD-/- stocks, the transmembrane domain is requi
red either to deliver the ectodomain to the appropriate intracellular compa
rtment or to form multimeric constructs which virtually reconstitute go thr
ough the interaction of transmembrane domains.