title: High conservation of herpes simplex virus UL5/UL52 helicase-primase complex in the era of new antiviral therapies.
abstract: The emergence of herpes simplex virus (HSV) resistance to current antiviral drugs, that all target the viral DNA polymerase, constitutes a major obstacle to antiviral treatment effectiveness of HSV infections, especially in immunocompromised patients. A novel and promising class of inhibitors of the HSV UL5/UL52 helicase-primase (HP) complex has been reported to hinder viral replication with a high potency. In this study, we describe the low natural polymorphism (interstrain identity >99.1% at both nucleotide and amino acid levels) of HSV HP complex subunits pUL5 and pUL52 among 64 HSV (32 HSV-1 and 32 HSV-2) clinical isolates, and we show that the HSV resistance profile to the first-line antiviral drug acyclovir (ACV) does not impact on the natural polymorphism of HSV HP complex. Genotypic tools and polymorphism data concerning HSV HP complex provided herein will be useful to detect drug resistance mutations in a relevant time frame when HP inhibitors (HPIs), i.e., amenamevir and pritelivir, will be available in medical practice.
authors.affiliation: Centre Hospitalier et Universitaire de Nantes, Service de Virologie, Nantes, France; EA4271 « Immunovirology and Genetic Polymorphism », Université de Nantes, France.
authors.forename: Marianne
authors.initials: M
authors.lastname: Collot
authors.affiliation: AP-HP, Hôpital Universitaire Antoine Béclère, Service de Microbiologie, Clamart, France; EA4043 - Unité Bactéries Pathogènes et Santé UFR de Pharmacie-Université Paris-Sud, France.
authors.forename: Caroline
authors.initials: C
authors.lastname: Rouard
authors.affiliation: AP-HP, Hôpitaux Universitaires Pitié-Salpêtrière-Charles Foix, Service de Virologie, Paris, France.
authors.forename: Christel
authors.initials: C
authors.lastname: Brunet
authors.affiliation: AP-HP, Hôpitaux Universitaires Pitié-Salpêtrière-Charles Foix, Service de Virologie, Paris, France; Sorbonne Universités, UPMC Univ Paris 06, CR7, Centre d'Immunologie et des Maladies Infectieuses (CIMI-Paris), INSERM U1135, Paris, France.
authors.forename: Henri
authors.initials: H
authors.lastname: Agut
authors.affiliation: AP-HP, Hôpitaux Universitaires Pitié-Salpêtrière-Charles Foix, Service de Virologie, Paris, France; Sorbonne Universités, UPMC Univ Paris 06, CR7, Centre d'Immunologie et des Maladies Infectieuses (CIMI-Paris), INSERM U1135, Paris, France.
authors.forename: David
authors.initials: D
authors.lastname: Boutolleau
authors.affiliation: AP-HP, Hôpitaux Universitaires Pitié-Salpêtrière-Charles Foix, Service de Virologie, Paris, France; Sorbonne Universités, UPMC Univ Paris 06, CR7, Centre d'Immunologie et des Maladies Infectieuses (CIMI-Paris), INSERM U1135, Paris, France. Electronic address: sonia.burrel@aphp.fr.
authors.forename: Sonia
authors.initials: S
authors.lastname: Burrel
mesh_terms: D000212:Acyclovir / Q000627:therapeutic use; D000998:Antiviral Agents / Q000627:therapeutic use*; D004265:DNA Helicases / Q000037:antagonists & inhibitors* / Q000235:genetics*; D019915:DNA Primase / Q000037:antagonists & inhibitors* / Q000235:genetics*; D024882:Drug Resistance, Viral; D018258:Herpesvirus 2, Human / Q000187:drug effects / Q000235:genetics* / Q000302:isolation & purification; D006801:Humans; D016867:Immunocompromised Host; D010069:Oxadiazoles / Q000627:therapeutic use*; D011110:Polymorphism, Genetic; D011725:Pyridines / Q000627:therapeutic use*; D018139:Simplexvirus / Q000187:drug effects / Q000235:genetics* / Q000302:isolation & purification; D013449:Sulfonamides; D013844:Thiazoles / Q000627:therapeutic use*; D014764:Viral Proteins / Q000037:antagonists & inhibitors* / Q000235:genetics*
chemical_list: C568714:ASP2151; D000998:Antiviral Agents; D010069:Oxadiazoles; D011725:Pyridines; D013449:Sulfonamides; D013844:Thiazoles; D014764:Viral Proteins; C453221:pritelivir; D019915:DNA Primase; C062021:helicase-primase, Human herpesvirus 1; D004265:DNA Helicases; D000212:Acyclovir
keywords: Antiviral resistance testing; Helicase-primase complex; Herpes simplex virus; Natural polymorphism