Drug-resistant herpes simplex virus in vitro and after acyclovir treatment in an immunocompromised patient

Abstract An unusually high incidence of acyclovir- and foscarnet-resistant herpes simplex virus (HSV) infection was noted after lymphocyte-depleted blood hematopoietic progenitor cell (HPC) transplantation from HLA-haploidentical family donors. Fourteen adults with hematologic malignancies underwent blood HPC transplantation from haploidentical family donors. Pheresis products were stringently depleted of T and B cells by immunomagnetic adsorption, and patients received no immunosuppression after transplantation. HSV reactivation occurred in all 7 evaluable HSV-1– or HSV-2–seropositive patients, at a median of 40 days after transplantation. Susceptibility testing of clinically resistant viral isolates demonstrated acyclovir resistance in all 5 cases tested. Second-line therapy produced only partial responses, and in vitro evidence of foscarnet resistance developed rapidly in all 3 patients treated with foscarnet. Healing of lesions coincided with T-cell recovery. The prolonged immunodeficiency associated with stringent lymphocyte depletion of the graft appears to strongly predispose to emergence of drug-resistant HSV. Furthermore, immune reconstitution is necessary for eradication of infection.

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Effect of discontinuous acyclovir treatment on in vitro reactivation of herpes simplex virus from latently infected trigeminal ganglia.

Antimicrobial Agents and Chemotherapy ◽

10.1128/aac.24.1.129 ◽

1983 ◽

Vol 24 (1) ◽

pp. 129-131 ◽

Cited By ~ 2

Author(s):

R J Klein ◽

A E Friedman-Kien ◽

E DeStefano

Keyword(s):

Herpes Simplex Virus ◽

Herpes Simplex ◽

Trigeminal Ganglia ◽

Acyclovir Treatment ◽

Latently Infected ◽

Simplex Virus

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Synergistic inhibition of drug-resistant and -sensitive herpes simplex virus in vitro by trifluorothymidine and interferon alpha

Antiviral Research ◽

10.1016/0166-3542(91)90226-h ◽

1991 ◽

Vol 15 ◽

pp. 117

Author(s):

C. Birch ◽

K. Hayes ◽

R. Doherty

Keyword(s):

Herpes Simplex Virus ◽

Herpes Simplex ◽

Interferon Alpha ◽

Drug Resistant ◽

Synergistic Inhibition ◽

Simplex Virus

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Effects of Analgesics on Delayed Postherpetic Pain in Mice

Anesthesiology ◽

10.1097/00000542-200205000-00021 ◽

2002 ◽

Vol 96 (5) ◽

pp. 1168-1174 ◽

Cited By ~ 34

Author(s):

Ichiro Takasaki ◽

Atsushi Sasaki ◽

Tsugunobu Andoh ◽

Hiroshi Nojima ◽

Kimiyasu Shiraki ◽

...

Keyword(s):

Herpes Simplex Virus ◽

Herpes Simplex ◽

Postherpetic Neuralgia ◽

Herpes Simplex Virus Infection ◽

Skin Lesions ◽

Cutaneous Lesions ◽

Acyclovir Treatment ◽

Simplex Virus ◽

Von Frey Filaments

Background Postherpetic neuralgia is pain that persists long after the disappearance of the cutaneous lesions of herpes zoster. However, the mechanisms of this delayed pain are unclear. Herpes simplex virus infection induces cutaneous lesions and pain-related responses in mice. The authors examined whether such responses would persist after the disappearance of the cutaneous lesions and whether some analgesics would be effective against them. Methods Female BALB/c mice were inoculated with herpes simplex virus type 1 on the unilateral hind paw. Pain-related responses of hind paw were determined using von Frey filaments. Beginning 5 days after inoculation, mice were given perorally the antiherpes agent acyclovir five times a day for 7 days. Effects of morphine (3-5 mg/kg subcutaneously), gabapentin (30-100 mg/kg perorally), mexiletine (10-30 mg/kg intraperitoneally), and diclofenac (30 mg/kg intraperitoneally) on pain-related responses were examined on days 25-35 after inoculation. Results Viral inoculation induced cutaneous lesions and pain-related responses beginning on day 5 after inoculation. Acyclovir treatment healed all skin lesions by day 15 after inoculation. Approximately half of the mice given acyclovir showed pain-related responses at least until day 40 after inoculation. Morphine, gabapentin, and mexiletine dose-dependently inhibited pain-related responses, but diclofenac had no effects. Conclusions The authors show a mouse model of delayed postherpetic pain. This may be useful for manifesting the mechanisms of postherpetic neuralgia and the factors contributing to the transition from acute herpetic pain to delayed postherpetic pain. This may also be useful for the development of new analgesics against postherpetic neuralgia.

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Antiviral Activity of the G-Quadruplex Ligand TMPyP4 against Herpes Simplex Virus-1

Viruses ◽

10.3390/v13020196 ◽

2021 ◽

Vol 13 (2) ◽

pp. 196

Author(s):

Sara Artusi ◽

Emanuela Ruggiero ◽

Matteo Nadai ◽

Beatrice Tosoni ◽

Rosalba Perrone ◽

...

Keyword(s):

Herpes Simplex Virus ◽

Dna Replication ◽

Herpes Simplex ◽

Antiviral Activity ◽

Herpes Simplex Virus 1 ◽

Tem Analysis ◽

Infected Cells ◽

Simplex Virus ◽

Hsv 1

The herpes simplex virus 1 (HSV-1) genome is extremely rich in guanine tracts that fold into G-quadruplexes (G4s), nucleic acid secondary structures implicated in key biological functions. Viral G4s were visualized in HSV-1 infected cells, with massive virus cycle-dependent G4-formation peaking during viral DNA replication. Small molecules that specifically interact with G4s have been shown to inhibit HSV-1 DNA replication. We here investigated the antiviral activity of TMPyP4, a porphyrin known to interact with G4s. The analogue TMPyP2, with lower G4 affinity, was used as control. We showed by biophysical analysis that TMPyP4 interacts with HSV-1 G4s, and inhibits polymerase progression in vitro; in infected cells, it displayed good antiviral activity which, however, was independent of inhibition of virus DNA replication or entry. At low TMPyP4 concentration, the virus released by the cells was almost null, while inside the cell virus amounts were at control levels. TEM analysis showed that virus particles were trapped inside cytoplasmatic vesicles, which could not be ascribed to autophagy, as proven by RT-qPCR, western blot, and immunofluorescence analysis. Our data indicate a unique mechanism of action of TMPyP4 against HSV-1, and suggest the unprecedented involvement of currently unknown G4s in viral or antiviral cellular defense pathways.

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