Characterization of an acyclovir-resistant herpes simplex virus type 2 strain isolated from a premature neonate

Ronda J. Oram; Daniel Marcellino; Daniel Strauss; Erik Gustafson; Christine L. Talarico; Adrienne K. Root; Prem L. Sharma; Ken Thompson; Joyce D. Fingeroth; Clyde Crumpacker; Betsy C. Herold

doi:10.1086/315387

Characterization of an acyclovir-resistant herpes simplex virus type 2 strain isolated from a premature neonate

Ronda J. Oram, Daniel Marcellino, Daniel Strauss, Erik Gustafson, Christine L. Talarico, Adrienne K. Root, Prem L. Sharma, Ken Thompson, Joyce D. Fingeroth, Clyde Crumpacker, Betsy C. Herold

Pediatrics

Research output: Contribution to journal › Article › peer-review

55 Scopus citations

Abstract

Acyclovir resistance is not a recognized problem among neonates with perinatal herpes simplex virus (HSV) infection. A premature newborn with neurocutaneous HSV infection was treated for 21 days with acyclovir. Disseminated disease recurred 8 days later. A recurrent isolate was resistant to acyclovir and lacked thymidine kinase activity on the basis of a frame- shift mutation in the thymidine kinase (tk) gene. Compared with the sensitive isolate obtained during primary infection, replication of the resistant isolate was reduced on primary and permanent cells and even further impaired on cells deleted for cellular tk. The resistant isolate lacked virulence in a murine model of genital infection. Acyclovir-resistant HSV-2 mutants can develop rapidly in neonatal infection and cause clinically significant disease, despite decreased replication in vitro and attenuated virulence in an animal model.

Original language	English (US)
Pages (from-to)	1458-1461
Number of pages	4
Journal	Journal of Infectious Diseases
Volume	181
Issue number	4
DOIs	https://doi.org/10.1086/315387
State	Published - 2000

ASJC Scopus subject areas

General Medicine

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This output contributes to the following UN Sustainable Development Goals (SDGs)

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10.1086/315387

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title = "Characterization of an acyclovir-resistant herpes simplex virus type 2 strain isolated from a premature neonate",

abstract = "Acyclovir resistance is not a recognized problem among neonates with perinatal herpes simplex virus (HSV) infection. A premature newborn with neurocutaneous HSV infection was treated for 21 days with acyclovir. Disseminated disease recurred 8 days later. A recurrent isolate was resistant to acyclovir and lacked thymidine kinase activity on the basis of a frame- shift mutation in the thymidine kinase (tk) gene. Compared with the sensitive isolate obtained during primary infection, replication of the resistant isolate was reduced on primary and permanent cells and even further impaired on cells deleted for cellular tk. The resistant isolate lacked virulence in a murine model of genital infection. Acyclovir-resistant HSV-2 mutants can develop rapidly in neonatal infection and cause clinically significant disease, despite decreased replication in vitro and attenuated virulence in an animal model.",

author = "Oram, {Ronda J.} and Daniel Marcellino and Daniel Strauss and Erik Gustafson and Talarico, {Christine L.} and Root, {Adrienne K.} and Sharma, {Prem L.} and Ken Thompson and Fingeroth, {Joyce D.} and Clyde Crumpacker and Herold, {Betsy C.}",

note = "Funding Information: Financial support: NIH (AI-36318 to B.C.H., CA-80935 to J.D.F., CA-85157 to E.G.); IDSA/Burroughs Wellcome (Young Investigator Award to B.C.H.).",

year = "2000",

doi = "10.1086/315387",

language = "English (US)",

volume = "181",

pages = "1458--1461",

journal = "Journal of Infectious Diseases",

issn = "0022-1899",

publisher = "Oxford University Press",

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T1 - Characterization of an acyclovir-resistant herpes simplex virus type 2 strain isolated from a premature neonate

AU - Oram, Ronda J.

AU - Marcellino, Daniel

AU - Strauss, Daniel

AU - Gustafson, Erik

AU - Talarico, Christine L.

AU - Root, Adrienne K.

AU - Sharma, Prem L.

AU - Thompson, Ken

AU - Fingeroth, Joyce D.

AU - Crumpacker, Clyde

AU - Herold, Betsy C.

N1 - Funding Information: Financial support: NIH (AI-36318 to B.C.H., CA-80935 to J.D.F., CA-85157 to E.G.); IDSA/Burroughs Wellcome (Young Investigator Award to B.C.H.).

PY - 2000

Y1 - 2000

N2 - Acyclovir resistance is not a recognized problem among neonates with perinatal herpes simplex virus (HSV) infection. A premature newborn with neurocutaneous HSV infection was treated for 21 days with acyclovir. Disseminated disease recurred 8 days later. A recurrent isolate was resistant to acyclovir and lacked thymidine kinase activity on the basis of a frame- shift mutation in the thymidine kinase (tk) gene. Compared with the sensitive isolate obtained during primary infection, replication of the resistant isolate was reduced on primary and permanent cells and even further impaired on cells deleted for cellular tk. The resistant isolate lacked virulence in a murine model of genital infection. Acyclovir-resistant HSV-2 mutants can develop rapidly in neonatal infection and cause clinically significant disease, despite decreased replication in vitro and attenuated virulence in an animal model.

AB - Acyclovir resistance is not a recognized problem among neonates with perinatal herpes simplex virus (HSV) infection. A premature newborn with neurocutaneous HSV infection was treated for 21 days with acyclovir. Disseminated disease recurred 8 days later. A recurrent isolate was resistant to acyclovir and lacked thymidine kinase activity on the basis of a frame- shift mutation in the thymidine kinase (tk) gene. Compared with the sensitive isolate obtained during primary infection, replication of the resistant isolate was reduced on primary and permanent cells and even further impaired on cells deleted for cellular tk. The resistant isolate lacked virulence in a murine model of genital infection. Acyclovir-resistant HSV-2 mutants can develop rapidly in neonatal infection and cause clinically significant disease, despite decreased replication in vitro and attenuated virulence in an animal model.

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Characterization of an acyclovir-resistant herpes simplex virus type 2 strain isolated from a premature neonate

Abstract

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UN SDGs

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