DOI: 10.1128/jvi.76.13.6718-6728.2002. Identification and Characterization of the UL56 Gene Product of Herpes Simplex Virus Type 2

Identification and Characterization of the UL56 Gene Product of Herpes Simplex Virus Type 2

10.1128/jvi.76.13.6718-6728.2002

Crossref journal-article

American Society for Microbiology

Journal of Virology (235)

Abstract

ABSTRACT The UL56 gene product of herpes simplex virus (HSV) has been shown to play an important role in viral pathogenicity. However, the properties and functions of the UL56 protein are little understood. We raised rabbit polyclonal antisera specific for the UL56 protein of HSV type 2 (HSV-2) and examined its expression and properties. The gene product was identified as three polypeptides with apparent molecular masses ranging from 32 to 35 kDa in HSV-2-infected cells, and at least one species was phosphorylated. Studies of their origins showed that the UL56 protein of HSV-2 is also translated from the upstream in-frame methionine codon that is not present in the HSV-1 genome. Synthesis was first detected at 6 h postinfection and was not abolished by the viral DNA synthesis inhibitor phosphonoacetic acid. Indirect immunofluorescence studies revealed that the UL56 protein localized to both the Golgi apparatus and cytoplasmic vesicles in HSV-2-infected and single UL56-expressing cells. Deletion mutant analysis showed that the C-terminal hydrophobic region of the protein was required for association with the cytoplasmic membrane and that the N-terminal proline-rich region was important for its translocation to the Golgi apparatus and cytoplasmic vesicles. Moreover, the results of protease digestion assays and sucrose gradient fractionation strongly suggested that UL56 is a tail-anchored type II membrane protein associated with lipid rafts. We thus hypothesized that the UL56 protein, as a tail-anchored type II membrane protein, may be involved in vesicular trafficking in HSV-2-infected cells.

Bibliography

Koshizuka, T., Goshima, F., Takakuwa, H., Nozawa, N., Daikoku, T., Koiwai, O., & Nishiyama, Y. (2002). Identification and Characterization of the UL56 Gene Product of Herpes Simplex Virus Type 2. Journal of Virology, 76(13), 6718â6728.

Authors 7

Tetsuo Koshizuka (first)
Fumi Goshima (additional)
Hiroki Takakuwa (additional)
Naoki Nozawa (additional)
Tohru Daikoku (additional)
Osamu Koiwai (additional)
Yukihiro Nishiyama (additional)

References 48 Referenced 66

10.1128/jvi.69.9.5560-5567.1995
10.1016/0042-6822(86)90128-5
10.1007/BF01379108
10.1073/pnas.94.25.13973
10.1128/JVI.72.6.4560-4570.1998
10.1128/JVI.74.2.834-845.2000
10.1128/JVI.74.10.4549-4561.2000
10.1128/JVI.73.5.4372-4384.1999
10.1006/bbrc.1997.7575
10.1146/annurev.cellbio.14.1.111
10.1073/pnas.90.7.2798
10.1073/pnas.091502398
10.1128/jvi.64.2.881-885.1990
10.1099/0022-1317-67-9-1759
10.1128/JVI.72.3.2010-2021.1998
10.1016/S0021-9258(18)47340-1
10.1016/0042-6822(86)90297-7
10.1128/JVI.75.3.1236-1251.2001
10.1016/0168-1702(96)80248-6
10.1016/0168-1702(94)90017-5
10.1023/A:1008053017716
10.1016/S0955-0674(97)80024-5
10.1016/0005-2736(85)90375-X
10.1083/jcb.115.4.887
10.1016/0006-291X(89)90767-5
10.1016/0962-8924(93)90066-A
10.1016/0022-2836(82)90515-0
10.1073/pnas.96.7.3734
10.1099/0022-1317-72-12-3057
10.1099/0022-1317-69-7-1531
10.1128/JVI.74.4.1827-1839.2000
Peles, E., H. Rosen, A. Rosen-Wölff, and Y. Becker. 1990. Importance of the HpaI-P sequence for herpes simplex virus-1 replication in the adrenal glands. Arch. Virol. 113 : 151-163. / Arch. Virol. (1990)
10.1073/pnas.93.21.11307
Roizman, B., and A. E. Sears. 1996. Herpes simplex viruses and their replication, p. 1043-1107. In B. N. Fields, D. M. Knipe, and P. M. Howley (ed.), Fields virology, 3rd ed. Lippincott-Raven, Philadelphia, Pa. / Fields virology (1996)
10.1128/JVI.74.1.117-129.2000
10.1016/0168-1702(86)90015-8
10.1007/BF02125037
10.1016/0168-1702(91)90076-8
10.1016/0168-1702(91)90099-H
10.1128/jvi.63.1.1-8.1989
10.1126/science.7660128
10.1099/0022-1317-81-10-2397
10.1038/42408
10.1016/0092-8674(88)90043-8
10.1016/0042-6822(92)90706-U
10.1083/jcb.200011146
10.1093/oxfordjournals.jbchem.a135561
10.1042/bj3360257

Dates

Type	When
Created	23 years ago (July 27, 2002, 6:09 a.m.)
Deposited	3 years, 5 months ago (March 5, 2022, 1:58 a.m.)
Indexed	2 weeks, 1 day ago (Aug. 6, 2025, 8:53 a.m.)
Issued	23 years, 1 month ago (July 1, 2002)
Published	23 years, 1 month ago (July 1, 2002)
Published Print	23 years, 1 month ago (July 1, 2002)

Funders 0

None

BibTeX

@article{Koshizuka_2002, title={Identification and Characterization of the UL56 Gene Product of Herpes Simplex Virus Type 2}, volume={76}, ISSN={1098-5514}, url={http://dx.doi.org/10.1128/jvi.76.13.6718-6728.2002}, DOI={10.1128/jvi.76.13.6718-6728.2002}, number={13}, journal={Journal of Virology}, publisher={American Society for Microbiology}, author={Koshizuka, Tetsuo and Goshima, Fumi and Takakuwa, Hiroki and Nozawa, Naoki and Daikoku, Tohru and Koiwai, Osamu and Nishiyama, Yukihiro}, year={2002}, month=jul, pages={6718–6728} }

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