Title

Genetic analysis of the role of herpes simplex virus type 1 glycoprotein K in infectious virus production and egress

Document Type

Article

Publication Date

1-1-1999

Abstract

Herpes simplex virus type 1 (KOS)ΔgK is a mutant virus which lacks glycoprotein K (gK) and exhibits defects in virion egress (S. Jayachandra, A. Baghian, and K. G. Kousoulas, J. Virol. 69:5401-5413, 1997). To further understand the role of gK in virus egress, we constructed recombinant viruses, ΔgKhpd-1, -2, -3, and -4, that specified gK amino-terminal portions of 139, 239, 268, and 326 amino acids, respectively, corresponding to truncations immediately after each of the four putative membrane-spanning domains of gK. ΔgKhpd-1 and ΔgKhpd-2 viruses produced lower yields and smaller plaques than ΔgK. Numerous ΔgKhpd-1 capsids accumulated predominately within large double-membrane vesicles of which the inner membrane appeared to be derived from viral envelopes while the outer membrane appeared to originate from the outer nuclear membrane. The mutant virus ΔgKhpd-3 produced higher yields and larger plaques than the ΔgK virus. The mutant virus ΔgKhpd-4 produced yields and plaques similar to those of the wild-type virus strain KOS, indicating that deletion of the carboxy-terminal 12 amino acids did not adversely affect virus replication and egress. Comparisons of the gK primary sequences specified by alphaherpesviruses revealed the presence of a cysteine-rich motif (CXXCC), located within domain Ill in the lumen side of gK, and a tyrosine-based motif, YTKΦ (where Φ is any bulky hydrophobic amino acid), located between the second and third hydrophobic domains (domain H) in the cytoplasmic side of gK. The mutant virus gK/Y183S, which was constructed to specify gK with a single-amino-acid change (Y to S) within the YTKΦ motif, replicated less efficiently than the ΔgK virus. The mutant virus gK/C304S-C307S, which was constructed to specify two serine instead of cysteine residues within the cysteine-rich motif (CXXCC changed to SXXSC) of gK domain III, replicated more efficiently than the ΔgK virus. Our data suggests that gK contains domains in its amino-terminal portion that promote aberrant nucleocapsid envelopment and/or membrane fusion between different virion envelopes and contains domains within its domains II and Ill that function in virus replication and egress.

Publication Source (Journal or Book title)

Journal of Virology

First Page

8457

Last Page

8468

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