FRINK Linked Data Fragments server

Matches in SemOpenAlex for { <https://semopenalex.org/work/W2066455965> ?p ?o ?g. }

• W2066455965 endingPage "2785" @default.
• W2066455965 startingPage "2775" @default.
• W2066455965 abstract "ABSTRACT Herpes simplex virus 1 (HSV-1) encodes Us3 protein kinase, which is critical for viral pathogenicity in both mouse peripheral sites (e.g., eyes and vaginas) and in the central nervous systems (CNS) of mice after intracranial and peripheral inoculations, respectively. Whereas some Us3 substrates involved in Us3 pathogenicity in peripheral sites have been reported, those involved in Us3 pathogenicity in the CNS remain to be identified. We recently reported that Us3 phosphorylated HSV-1 dUTPase (vdUTPase) at serine 187 (Ser-187) in infected cells, and this phosphorylation promoted viral replication by regulating optimal enzymatic activity of vdUTPase. In the present study, we show that the replacement of vdUTPase Ser-187 by alanine (S187A) significantly reduced viral replication and virulence in the CNS of mice following intracranial inoculation and that the phosphomimetic substitution at vdUTPase Ser-187 in part restored the wild-type viral replication and virulence. Interestingly, the S187A mutation in vdUTPase had no effect on viral replication and pathogenic effects in the eyes and vaginas of mice after ocular and vaginal inoculation, respectively. Similarly, the enzyme-dead mutation in vdUTPase significantly reduced viral replication and virulence in the CNS of mice after intracranial inoculation, whereas the mutation had no effect on viral replication and pathogenic effects in the eyes and vaginas of mice after ocular and vaginal inoculation, respectively. These observations suggested that vdUTPase was one of the Us3 substrates responsible for Us3 pathogenicity in the CNS and that the CNS-specific virulence of HSV-1 involved strict regulation of vdUTPase activity by Us3 phosphorylation. IMPORTANCE Herpes simplex virus 1 (HSV-1) encodes a viral protein kinase Us3 which is critical for pathogenicity both in peripheral sites and in the central nervous systems (CNS) of mice following peripheral and intracranial inoculations, respectively. Whereas some Us3 substrates involved in Us3 pathogenicity in peripheral sites have been reported, those involved in Us3 pathogenicity in the CNS remain to be identified. Here, we report that Us3 phosphorylation of viral dUTPase (vdUTPase) at serine 187 (Ser-187), which has been shown to promote the vdUTPase activity, appears to be critical for viral virulence in the CNS but not for pathogenic effects in peripheral sites. Since HSV proteins critical for viral virulence in the CNS are, in almost all cases, also involved in viral pathogenicity at peripheral sites, this phosphorylation event is a unique report of a specific mechanism involved in HSV-1 virulence in the CNS." @default.
• W2066455965 created "2016-06-24" @default.
• W2066455965 creator A5005243857 @default.
• W2066455965 creator A5045399700 @default.
• W2066455965 creator A5062366510 @default.
• W2066455965 creator A5089923617 @default.
• W2066455965 date "2014-03-01" @default.
• W2066455965 modified "2023-10-18" @default.
• W2066455965 title "Phosphorylation of a Herpes Simplex Virus 1 dUTPase by a Viral Protein Kinase, Us3, Dictates Viral Pathogenicity in the Central Nervous System but Not at the Periphery" @default.
• W2066455965 cites W1495845650 @default.
• W2066455965 cites W1502150553 @default.
• W2066455965 cites W1553195773 @default.
• W2066455965 cites W1567366091 @default.
• W2066455965 cites W1588142026 @default.
• W2066455965 cites W1608386732 @default.
• W2066455965 cites W1720083525 @default.
• W2066455965 cites W1812947354 @default.
• W2066455965 cites W1948895965 @default.
• W2066455965 cites W1965635445 @default.
• W2066455965 cites W1966885880 @default.
• W2066455965 cites W1970010476 @default.
• W2066455965 cites W1977847296 @default.
• W2066455965 cites W1978155015 @default.
• W2066455965 cites W1980477679 @default.
• W2066455965 cites W1984116579 @default.
• W2066455965 cites W1986791214 @default.
• W2066455965 cites W1993881377 @default.
• W2066455965 cites W1993942283 @default.
• W2066455965 cites W1994882633 @default.
• W2066455965 cites W2005210883 @default.
• W2066455965 cites W2007628037 @default.
• W2066455965 cites W2008631953 @default.
• W2066455965 cites W2009610199 @default.
• W2066455965 cites W2020897806 @default.
• W2066455965 cites W2029248995 @default.
• W2066455965 cites W2033439739 @default.
• W2066455965 cites W2036787105 @default.
• W2066455965 cites W2038652104 @default.
• W2066455965 cites W2042144075 @default.
• W2066455965 cites W2042753412 @default.
• W2066455965 cites W2043238718 @default.
• W2066455965 cites W2053005562 @default.
• W2066455965 cites W2053800551 @default.
• W2066455965 cites W2065840126 @default.
• W2066455965 cites W2068813825 @default.
• W2066455965 cites W2072687295 @default.
• W2066455965 cites W2072945014 @default.
• W2066455965 cites W2074901911 @default.
• W2066455965 cites W2078302353 @default.
• W2066455965 cites W2082779452 @default.
• W2066455965 cites W2084268304 @default.
• W2066455965 cites W2087846171 @default.
• W2066455965 cites W2094400633 @default.
• W2066455965 cites W2096194507 @default.
• W2066455965 cites W2102844419 @default.
• W2066455965 cites W2103062754 @default.
• W2066455965 cites W2103817756 @default.
• W2066455965 cites W2107380406 @default.
• W2066455965 cites W2109863815 @default.
• W2066455965 cites W2115213823 @default.
• W2066455965 cites W2119628526 @default.
• W2066455965 cites W2120791711 @default.
• W2066455965 cites W2122800938 @default.
• W2066455965 cites W2123900264 @default.
• W2066455965 cites W2124219221 @default.
• W2066455965 cites W2125553816 @default.
• W2066455965 cites W2131027478 @default.
• W2066455965 cites W2135433503 @default.
• W2066455965 cites W2135814779 @default.
• W2066455965 cites W2138368591 @default.
• W2066455965 cites W2138395245 @default.
• W2066455965 cites W2140938030 @default.
• W2066455965 cites W2141673999 @default.
• W2066455965 cites W2142293654 @default.
• W2066455965 cites W2146912995 @default.
• W2066455965 cites W2147469769 @default.
• W2066455965 cites W2149279386 @default.
• W2066455965 cites W2150241121 @default.
• W2066455965 cites W2151781175 @default.
• W2066455965 cites W2156472127 @default.
• W2066455965 cites W2162510249 @default.
• W2066455965 cites W2162557708 @default.
• W2066455965 cites W2168890635 @default.
• W2066455965 cites W2169975488 @default.
• W2066455965 cites W2171848502 @default.
• W2066455965 cites W2172305558 @default.
• W2066455965 cites W2317301596 @default.
• W2066455965 doi "https://doi.org/10.1128/jvi.03300-13" @default.
• W2066455965 hasPubMedCentralId "https://www.ncbi.nlm.nih.gov/pmc/articles/3958095" @default.
• W2066455965 hasPubMedId "https://pubmed.ncbi.nlm.nih.gov/24352467" @default.
• W2066455965 hasPublicationYear "2014" @default.
• W2066455965 type Work @default.
• W2066455965 sameAs 2066455965 @default.
• W2066455965 citedByCount "21" @default.
• W2066455965 countsByYear W20664559652014 @default.
• W2066455965 countsByYear W20664559652015 @default.
• W2066455965 countsByYear W20664559652016 @default.
• W2066455965 countsByYear W20664559652017 @default.

• next