HSV-1 and HSV-2 Seroprevalence in the United States among Asymptomatic Women Unaware of Any Herpes Simplex Virus Infection (Herpevac Trial for Women)

Schulte, Joann; Bellamy, Abbie R.; Hook, Edward W.; Bernstein, David I.; Levin, Myron J.; Leone, Peter A.; Sokol-Anderson, Marcia L.; Ewell, Marian; Wolff, Peter; Heineman, Thomas C.; Belshe, Robert B.

doi:10.1097/smj.0000000000000062

Cited by 22 publications

(19 citation statements)

References 1 publication

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“…Etiologically, HSV-1 is associated with gingivostomatitis, herpetic stromal keratitis, and anogenital lesions, while HSV-2, the primary agent of ulcerative anogenital lesions, infects ∼20% of individuals in the United States and has been documented to increase the frequency of human immunodeficiency virus (HIV) acquisition. 1 DNA polymerase has been the primary HSV antiviral target, exemplified by the deoxyguanosine analogue acyclovir (ACV), the drug of choice for almost 40 years. 2 However, an increased incidence of ACV-refractory HSV keratitis, a leading cause of corneal morbidity in industrialized countries, has been reported.…”

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confidence: 99%

Characterization of the C-Terminal Nuclease Domain of Herpes Simplex Virus pUL15 as a Target of Nucleotidyltransferase Inhibitors

et al. 2016

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The natural product α-hydroxytropolones manicol and β-thujaplicinol inhibit replication of herpes simplex viruses 1 and 2 (HSV-1 and HSV-2, respectively) at nontoxic concentrations. Because these were originally developed as divalent metal-sequestering inhibitors of the ribonuclease H activity of HIV-1 reverse transcriptase, α-hydroxytropolones likely target related HSV proteins of the nucleotidyltransferase (NTase) superfamily, which share an “RNase H-like” fold. One potential candidate is pUL15, a component of the viral terminase molecular motor complex, whose C-terminal nuclease domain, pUL15C, has recently been crystallized. Crystallography also provided a working model for DNA occupancy of the nuclease active site, suggesting potential protein–nucleic acid contacts over a region of ∼14 bp. In this work, we extend crystallographic analysis by examining pUL15C-mediated hydrolysis of short, closely related DNA duplexes. In addition to defining a minimal substrate length, this strategy facilitated construction of a dual-probe fluorescence assay for rapid kinetic analysis of wild-type and mutant nucleases. On the basis of its proposed role in binding the phosphate backbone, studies with pUL15C variant Lys700Ala showed that this mutation affected neither binding of duplex DNA nor binding of small molecule to the active site but caused a 17-fold reduction in the turnover rate (kcat), possibly by slowing conversion of the enzyme–substrate complex to the enzyme–product complex and/or inhibiting dissociation from the hydrolysis product. Finally, with a view of pUL15-associated nuclease activity as an antiviral target, the dual-probe fluorescence assay, in combination with differential scanning fluorimetry, was used to demonstrate inhibition by several classes of small molecules that target divalent metal at the active site.

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confidence: 99%

Characterization of the C-Terminal Nuclease Domain of Herpes Simplex Virus pUL15 as a Target of Nucleotidyltransferase Inhibitors

et al. 2016

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“…16,44 Notably, many HSV-seropositive AYA are unaware of their infection. 45 In HSV outbreaks, ulcerative lesions may appear anywhere on the genital, anal, or oral mucosa and are characterized as painful, shallow, and often multiple. They are typically associated with lymphadenopathy that may be bilateral.…”

Section: Sexually Transmitted Infections In Lesbian Gay Bisexual Tmentioning

confidence: 99%

Human Immunodeficiency Virus, Other Sexually Transmitted Infections, and Sexual and Reproductive Health in Lesbian, Gay, Bisexual, Transgender Youth

Wood

Salas-Humara²,

Dowshen

2016

Pediatric Clinics of North America

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“…However, this Herpevac cohort was nearly five times larger and was composed entirely of individuals denying any previous symptomatic HSV infection [24]. Collectively, these studies indicate that fewer children and adolescents are infected with HSV-1 today than in previous decades possibly due to delayed exposure to the virus.…”

Section: Epidemiologic Insightsmentioning

confidence: 99%

The current state of vaccine development for ocular HSV-1 infection

Royer

Cohen

Carr

2015

Expert Review of Ophthalmology

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Summary HSV-1 continues to be the leading cause of infectious corneal blindness. Clinical trials for vaccines against genital HSV infection have been ongoing for more than three decades. Despite this, no approved vaccine exists, and no formal clinical trials have evaluated the impact of HSV vaccines on eye health. We review here the current state of development for an efficacious HSV-1 vaccine and call for involvement of ophthalmologists and vision researchers.

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HSV-1 and HSV-2 Seroprevalence in the United States among Asymptomatic Women Unaware of Any Herpes Simplex Virus Infection (Herpevac Trial for Women)

Cited by 22 publications

References 1 publication

Characterization of the C-Terminal Nuclease Domain of Herpes Simplex Virus pUL15 as a Target of Nucleotidyltransferase Inhibitors

Characterization of the C-Terminal Nuclease Domain of Herpes Simplex Virus pUL15 as a Target of Nucleotidyltransferase Inhibitors

Human Immunodeficiency Virus, Other Sexually Transmitted Infections, and Sexual and Reproductive Health in Lesbian, Gay, Bisexual, Transgender Youth

The current state of vaccine development for ocular HSV-1 infection

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