Novel Therapy Combines Herpes Simplex Virus With Genes Encoding Immunomodulatory Proteins

ACS Omega ◽  
2020 ◽  
Vol 5 (38) ◽  
pp. 24329-24339
Author(s):  
Margaux Fresnais ◽  
Rémi Longuespée ◽  
Max Sauter ◽  
Torsten Schaller ◽  
Michaela Arndt ◽  
...  

1991 ◽  
Vol 72 (4) ◽  
pp. 897-906 ◽  
Author(s):  
C. A. MacLean ◽  
S. Efstathiou ◽  
M. L. Elliott ◽  
F. E. Jamieson ◽  
D. J. McGeoch

2002 ◽  
Vol 76 (22) ◽  
pp. 11469-11475 ◽  
Author(s):  
Guoying Zhou ◽  
Bernard Roizman

ABSTRACT Earlier studies have shown that herpes simplex virus 1 (HSV-1) virions of mutant lacking glycoprotein D (gD) and made in either complementing (gD−/+ stocks) or noncomplementing cells (gD−/− stocks) induce apoptosis. Subsequent studies have shown that apoptosis induced by gD−/− mutant virus stocks can be blocked by in trans delivery of viral genes that encode either intact gD or a mixture of two genes encoding the glycoprotein ectodomain plus transmembrane domain (gD-B) and transmembrane domain plus the cytoplasmic carboxyl terminus of the protein (gD-D), respectively. Since the presence of the transmembrane domains was critical for precluding apoptosis in the bipartite system, the question arose whether the two components, gD-B and gD-D, form a heterodimer mediated by an unpaired cysteine located in the transmembrane domain. We report the following. (i) The substitution of the unpaired cysteine with serine in either gD-B or gD-D truncated forms of gD disabled the ability of gD-D and gD-B to block apoptosis. (ii) Immunoprecipitation of gD-D coprecipitated gD-B only from lysates of cells transduced with gD-D and gD-B containing the cysteine in the transmembrane domains. Replacement of cysteine with serine ablated coprecipitation of the components. (ii) The mixture of gD-D and gD-B complemented at a low level gD−/+ virions. We conclude that the gD-B and gD-D can form a heterodimer dependent on the presence of cysteines in the transmembrane domain and the heterodimer can substitute for intact gD but at a much reduced efficiency.


1998 ◽  
Vol 72 (3) ◽  
pp. 2010-2021 ◽  
Author(s):  
Aidan Dolan ◽  
Fiona E. Jamieson ◽  
Charles Cunningham ◽  
Barbara C. Barnett ◽  
Duncan J. McGeoch

ABSTRACT The genomic DNA sequence of herpes simplex virus type 2 (HSV-2) strain HG52 was determined as 154,746 bp with a G+C content of 70.4%. A total of 74 genes encoding distinct proteins was identified; three of these were each present in two copies, within major repeat elements of the genome. The HSV-2 gene set corresponds closely with that of HSV-1, and the HSV-2 sequence prompted several local revisions to the published HSV-1 sequence (D. J. McGeoch, M. A. Dalrymple, A. J. Davison, A. Dolan, M. C. Frame, D. McNab, L. J. Perry, J. E. Scott, and P. Taylor, J. Gen. Virol. 69:1531–1574, 1988). No compelling evidence for the existence of any additional protein-coding genes in HSV-2 was identified.


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