Input of recombinant phenotyping for the characterization of a novel acyclovir-resistance mutation identified in a patient with recurrent herpetic keratitis

Robinet-Perrin, Antoine; Tumiotto, Camille; Cornut, Thomas; Santoni, A; Touboul, David; Goupil-Gouyette, Thibaud; Garrigue, Isabelle; Boutolleau, David; Burrel, Sonia

doi:10.1016/j.antiviral.2019.06.007

Cited by 8 publications

(3 citation statements)

References 11 publications

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“…None of the other TK or UL30 SNPs found in the dataset were known to be associated with drug resistance when compared with the current literature. 24 , 25 , 62 , 63 To better visualize how the novel SNPs in TK and UL30 may affect structure or function, the novel SNPs were mapped both to previously determined crystal structures as well as alphafold2 protein prediction. Alphafold2 prediction was used because some of the SNPs are located in uncrystallized areas.…”

Section: Resultsmentioning

confidence: 99%

Phylogenetic and Genomic Characterization of Whole Genome Sequences of Ocular Herpes Simplex Virus Type 1 Isolates Identifies Possible Virulence Determinants in Humans

Chau

Kolb

Miller

et al. 2023

Invest. Ophthalmol. Vis. Sci.

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Purpose There are limited data on the prevalence and genetic diversity of herpes simplex virus type 1 (HSV-1) virulence genes in ocular isolates. Here, we sequenced 36 HSV-1 ocular isolates, collected by the Bascom Palmer Eye Institute, a university-based eye hospital, from three different ocular anatomical sites (conjunctiva, cornea, and eyelid) and carried out a genomic and phylogenetic analyses. Methods The PacBio Sequel II long read platform was used for genome sequencing. Phylogenetic analysis and genomic analysis were performed to help better understand genetic variability among common virulence genes in ocular herpetic disease. Results A phylogenetic network generated using the genome sequences of the 36 Bascom Palmer ocular isolates, plus 174 additional strains showed that ocular isolates do not group together phylogenetically. Analysis of the thymidine kinase and DNA polymerase protein sequences from the Bascom Palmer isolates showed multiple novel single nucleotide polymorphisms, but only one, BP-K14 encoded a known thymidine kinase acyclovir resistance mutation. An analysis of the multiple sequence alignment comprising the 51 total ocular isolates versus 159 nonocular strains detected several possible single nucleotide polymorphisms in HSV-1 genes that were found significantly more often in the ocular isolates. These genes included UL6, gM, VP19c, VHS, gC, VP11/12, and gG. Conclusions There does not seem to be a specific genetic feature of viruses causing ocular infection. The identification of novel and common recurrent polymorphisms may help to understand the drivers of herpetic pathogenicity and specific factors that may influence the virulence of ocular disease.

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Section: Resultsmentioning

confidence: 99%

Phylogenetic and Genomic Characterization of Whole Genome Sequences of Ocular Herpes Simplex Virus Type 1 Isolates Identifies Possible Virulence Determinants in Humans

Chau

Kolb

Miller

et al. 2023

Invest. Ophthalmol. Vis. Sci.

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“…Antiviral resistance of HSK is generating concern, but the exact mechanisms of resistance have not been fully articulated[ 168 ]. Acyclovir is the most common drug used in the management of HSK[ 169 ], although eyedrops are now being proposed[ 170 ].…”

Section: Antiviral Therapy For Herpes Simplex Keratitis: Efficacy And...mentioning

confidence: 99%

Herpes simplex keratitis: A brief clinical overview

Musa,

Enaholo,

Aluyi-Osa

et al. 2024

World J Virol

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The aim of our minireview is to provide a brief overview of the diagnosis, clinical aspects, treatment options, management, and current literature available regarding herpes simplex keratitis (HSK). This type of corneal viral infection is caused by the herpes simplex virus (HSV), which can affect several tissues, including the cornea. One significant aspect of HSK is its potential to cause recurrent episodes of inflammation and damage to the cornea. After the initial infection, the HSV can establish a latent infection in the trigeminal ganglion, a nerve cluster near the eye. The virus may remain dormant for extended periods. Periodic reactivation of the virus can occur, leading to recurrent episodes of HSK. Factors triggering reactivation include stress, illness, immunosuppression, or trauma. Recurrent episodes can manifest in different clinical patterns, ranging from mild epithelial involvement to more severe stromal or endothelial disease. The severity and frequency of recurrences vary among individuals. Severe cases of HSK, especially those involving the stroma and leading to scarring, can result in vision impairment or even blindness in extreme cases. The cornea's clarity is crucial for good vision, and scarring can compromise this, potentially leading to visual impairment. The management of HSK involves not only treating acute episodes but also implementing long-term strategies to prevent recurrences and attempt repairs of corneal nerve endings via neurotization. Antiviral medications, such as oral Acyclovir or topical Ganciclovir, may be prescribed for prophylaxis. The immune response to the virus can contribute to corneal damage. Inflammation, caused by the body's attempt to control the infection, may inadvertently harm the corneal tissues. Clinicians should be informed about triggers and advised on measures to minimize the risk of reactivation. In summary, the recurrent nature of HSK underscores the importance of both acute and long-term management strategies to preserve corneal health and maintain optimal visual function.

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“…Plus récemment, la solution permettant de facilement créer des virus recombinants est apparue en détournant la machinerie bactérienne. L'utilisation de virus recombinants produits en utilisant un système de chromosome artificiel bactérien (bacterial artificial chromosome, BAC) a été développé récemment pour HSV dans le cadre de la résistance aux antiviraux [90][91][92] sur le modèle des travaux effectués sur le cytomégalovirus (CMV) [93][94][95][96]. En effet, le clonage des génomes viraux entiers dans des vecteurs de type BAC est possible et permet de manipuler ces génomes en utilisant les systèmes de recombinaison présents chez les bactéries, notamment Escherichia coli.…”

Section: Utilisation Des Virus Recombinantsunclassified

Herpes simplex virus resistance to antivirals

Burrel¹,

Topalis²,

Boutolleau³

2020

Virologie

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Herpes simplex virus (HSV) infections remain an important cause of morbidity among immunocompromised patients, such as transplant recipients and human immunodeficiency virus [HIV]-infected individuals. Only few antiviral drugs are available to treat HSV infections: (val)acyclovir, foscarnet, and cidofovir. Prophylactic and curative antiviral treatments administered during prolonged periods among patients with altered T-cell immunity may lead to the emergence of HSV resistance to antivirals, contributing to a challenging therapeutic management of viral infection. The persistence of herpetic lesions after 10 days of well-conducted antiviral therapy is suggestive of viral resistance. Resistance to antivirals can be detected using genotypic methods (identifications of antiviral resistance-associated mutations by sequencing genes encoding viral proteins involved in the mechanism of action of antivirals) or phenotypic methods (measure of antiviral drug concentration inhibiting 50% of viral replication in cell culture). The prevalence of HSV resistance to acyclovir is below 1% in immunocompetent individuals, except those with herpetic keratitis for whom prevalence can reach 7%, and varies from 3.5% to 11% in immunocompromised patients. Adverse effects and the absence of eradication of viral latent infection constitute other limits to the use of antiviral drugs. New antiviral compounds undergoing clinical trials and novel potential viral targets seem very promising to enlarge the panel of efficient compound to treat HSV infections.

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Input of recombinant phenotyping for the characterization of a novel acyclovir-resistance mutation identified in a patient with recurrent herpetic keratitis

Cited by 8 publications

References 11 publications

Phylogenetic and Genomic Characterization of Whole Genome Sequences of Ocular Herpes Simplex Virus Type 1 Isolates Identifies Possible Virulence Determinants in Humans

Phylogenetic and Genomic Characterization of Whole Genome Sequences of Ocular Herpes Simplex Virus Type 1 Isolates Identifies Possible Virulence Determinants in Humans

Herpes simplex keratitis: A brief clinical overview

Herpes simplex virus resistance to antivirals

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