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 frameshift 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.

Mandelic Acid Condensation Polymer: Novel Candidate Microbicide for Prevention of Human Immunodeficiency Virus and Herpes Simplex Virus Entry

“…DT-1 and DT-2 are acyclovir-sensitive and -resistant strains, respectively, isolated from a neonate (28). Adenovirus type 5 (Ad5) was obtained from ATCC.…”

Persistence of herpes simplex virus DNA in cerebrospinal fluid of neonates with herpes simplex virus encephalitis

“…This latter infant also had a positive CSF HSV PCR at 48 h after completion of the initial 21 days of acyclovir. 26 In addition, acyclovir resistance was reported in an infant who had a cutaneous HSV-2 recurrence 36 h after cessation of 6 months of acyclovir suppression. 27 These cases highlight the importance of obtaining herpes culture or performing genotypic characterization of PCR products for acyclovir resistance testing in infants who do not respond appropriately to acyclovir therapy, have frequent recurrences while on acyclovir suppressive therapy or were born to mothers who received prolonged acyclovir suppression during pregnancy.…”

Point Mutations and Antiviral Drug Resistance

“…However, herpes-resistance to antiviral drugs is well established (7-14%) in imunocompromised patients (Griffiths, 2009;Chen et al, 2000;Levin et al, 2004;Safrin et al, 1994) and neonates (Levin et al, 2001;Nyquist et al, 1994;Oram et al, 2000). It has been found that the most significant risk factors to developing antiviral-resistance are the degree of immunosuppression and prolonged exposure to the antiviral agent (Levin et al, 2004).…”

“…In immunocompetent individuals the immune response can rapidly dealt with the viral mutants before they can become clinically apparent (Coen, 1994). However, it is not always the case, it has been published that acyclovir-resistant HSV-2 mutants can be developed rapidly in neonatal infection and cause clinically significant disease, in spite of the in vitro decreased replication and attenuated virulence in an animal model showed by the viral strain (Oram, 2000). 2.…”