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Gene Review

US3  -  tegument protein; phosphorylates nuclear...

Human herpesvirus 1

 
 
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Disease relevance of US3

  • Herpes simplex virus 1 ICP22 regulates the accumulation of a shorter mRNA and of a truncated US3 protein kinase that exhibits altered functions [1].
  • ORF 2 is 471 aa long and could encode a protein of 53.8 kDa which shared aa homology with the protein kinases encoded by HSV-1 US3 and its gene homologs [2].
  • Furthermore, the US3 kinase affects the morphology of primary envelopment such that in its absence, UL34 protein-containing enveloped virions accumulate within membrane-bound vesicles [3].
  • The herpes simplex virus type 1 (HSV-1) US3 kinase is likely important for primary envelopment of progeny nucleocapsids since it localizes to the nuclear envelope of infected cells and largely determines the phosphorylation state and localization of the necessary primary envelopment factor, the UL34 protein [3].
  • These results indicate that the HSV-2 UL13 PK had unique catalytic properties different from those of cellular CK I, CK II, and the viral PK encoded by the US3 gene [4].
 

High impact information on US3

 

Chemical compound and disease context of US3

  • One gene, designated B1R, encodes a 34.2K protein which shares 27% identity with a protein kinase encoded by the herpes simplex virus type 1 US3 gene and contains conserved motifs characteristic of protein kinases of serine/threonine specificity [9].
 

Biological context of US3

 

Anatomical context of US3

  • US3 deletion caused (i) virion accumulation in nuclear membrane invaginations, (ii) delayed virus production onset, and (iii) reduced peak virus titers [12].
  • For this report, recombinant viruses were constructed to determine the significance of UL34 protein phosphorylation and US3 catalytic activity on UL34 protein localization, single-step growth, and envelopment morphology in both HEp-2 and Vero cells [3].
  • Viral antigen-positive neurons were strictly confined to the ipsilateral spinal trigeminal nucleus in mice corneally infected with the US3 PK- mutant [13].
  • The transneuronal spread of a virulent wild-type herpes simplex virus type 2 (HSV-2) and its US3 protein kinase-deficient (US3 PK-) mutant was immunohistochemically studied in mice after inoculations into the cornea, anterior chamber, tongue, and masseter muscle [13].
 

Other interactions of US3

 

Analytical, diagnostic and therapeutic context of US3

References

  1. Herpes simplex virus 1 ICP22 regulates the accumulation of a shorter mRNA and of a truncated US3 protein kinase that exhibits altered functions. Poon, A.P., Roizman, B. J. Virol. (2005) [Pubmed]
  2. Nucleotide sequence analysis of an infectious laryngotracheitis virus gene corresponding to the US3 of HSV-1 and a unique gene encoding a 67 kDa protein. Kongsuwan, K., Prideaux, C.T., Johnson, M.A., Sheppard, M., Rhodes, S. Arch. Virol. (1995) [Pubmed]
  3. Herpes simplex virus type 1 primary envelopment: UL34 protein modification and the US3-UL34 catalytic relationship. Ryckman, B.J., Roller, R.J. J. Virol. (2004) [Pubmed]
  4. Purification and characterization of the protein kinase encoded by the UL13 gene of herpes simplex virus type 2. Daikoku, T., Shibata, S., Goshima, F., Oshima, S., Tsurumi, T., Yamada, H., Yamashita, Y., Nishiyama, Y. Virology (1997) [Pubmed]
  5. ICP0 and the US3 protein kinase of herpes simplex virus 1 independently block histone deacetylation to enable gene expression. Poon, A.P., Gu, H., Roizman, B. Proc. Natl. Acad. Sci. U.S.A. (2006) [Pubmed]
  6. Herpes simplex virus protein kinase US3 activates and functionally overlaps protein kinase A to block apoptosis. Benetti, L., Roizman, B. Proc. Natl. Acad. Sci. U.S.A. (2004) [Pubmed]
  7. The US3 protein kinase of herpes simplex virus 1 mediates the posttranslational modification of BAD and prevents BAD-induced programmed cell death in the absence of other viral proteins. Munger, J., Roizman, B. Proc. Natl. Acad. Sci. U.S.A. (2001) [Pubmed]
  8. Herpes simplex virus 1 induces and blocks apoptosis at multiple steps during infection and protects cells from exogenous inducers in a cell-type-dependent manner. Galvan, V., Roizman, B. Proc. Natl. Acad. Sci. U.S.A. (1998) [Pubmed]
  9. Two early vaccinia virus genes encode polypeptides related to protein kinases. Howard, S.T., Smith, G.L. J. Gen. Virol. (1989) [Pubmed]
  10. The herpes simplex virus 1 protein kinase encoded by the US3 gene mediates posttranslational modification of the phosphoprotein encoded by the UL34 gene. Purves, F.C., Spector, D., Roizman, B. J. Virol. (1991) [Pubmed]
  11. The herpes simplex virus 1 protein kinase US3 is required for protection from apoptosis induced by the virus. Leopardi, R., Van Sant, C., Roizman, B. Proc. Natl. Acad. Sci. U.S.A. (1997) [Pubmed]
  12. Ultrastructural localization of the herpes simplex virus type 1 UL31, UL34, and US3 proteins suggests specific roles in primary envelopment and egress of nucleocapsids. Reynolds, A.E., Wills, E.G., Roller, R.J., Ryckman, B.J., Baines, J.D. J. Virol. (2002) [Pubmed]
  13. Immunohistochemical studies on the transneuronal spread of virulent herpes simplex virus type 2 and its US3 protein kinase-deficient mutant after ocular inoculation. Yamamoto, M., Kurachi, R., Morishima, T., Kito, J., Nishiyama, Y. Microbiol. Immunol. (1996) [Pubmed]
  14. UL13 protein kinase of herpes simplex virus 1 complexes with glycoprotein E and mediates the phosphorylation of the viral Fc receptor: glycoproteins E and I. Ng, T.I., Ogle, W.O., Roizman, B. Virology (1998) [Pubmed]
  15. Nucleotide sequence of canine herpesvirus homologues of herpes simplex virus type 1 US2, US3, glycoproteins I and E, US8.5 and US9 genes. Tyack, S.G., Studdert, M.J., Johnson, M.A. DNA Seq. (1997) [Pubmed]
  16. Herpes simplex virus 1 protein kinase is encoded by open reading frame US3 which is not essential for virus growth in cell culture. Purves, F.C., Longnecker, R.M., Leader, D.P., Roizman, B. J. Virol. (1987) [Pubmed]
  17. Purification and biochemical characterization of the protein kinase encoded by the US3 gene of herpes simplex virus type 2. Daikoku, T., Yamashita, Y., Tsurumi, T., Maeno, K., Nishiyama, Y. Virology (1993) [Pubmed]
  18. The antiviral xanthate compound D609 inhibits herpes simplex virus type 1 replication and protein phosphorylation. Walro, D.G., Rosenthal, K.S. Antiviral Res. (1997) [Pubmed]
 
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