Persistent viral DNA detection in blood after primary herpes simplex 1 infection revealed by hepatitis with hemophagocytic syndrome

Alidjinou, Enagnon Kazali; Dewilde, A.; Terriou, Louis; Lazrek, Mouna; Hober, Didier

doi:10.1016/j.jcv.2015.06.087

Cited by 7 publications

(4 citation statements)

References 22 publications

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“…To our knowledge, six cases of HSV-1 induced HLH have been previously reported in adults, only two of which were fatal. [6][7][8][9][10][11] Drori et al 6 describe the case of a 50-year-old man with a past medical history significant for diabetes mellitus who initially presented as an outpatient with fever, leukopenia, and dyspnea. Despite the antibiotic treatment and a negative infectious workup, his condition deteriorated over the next week and he was admitted to the hospital with fever, hyperferritinemia, and acute liver and kidney failure.…”

Section: Discussionmentioning

confidence: 99%

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Herpes simplex virus-1 triggered hemophagocytic lymphohistiocytosis in a patient with granulomatosis with polyangiitis

States¹,

Kapp²

2022

Autops Case Rep

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Hemophagocytic lymphohistiocytosis (HLH) is a rare, aggressive hyperinflammatory syndrome in which an inciting event triggers massive, uninhibited activation of T lymphocytes and macrophages. Although viral infections are the most common trigger of HLH, cases of HSV-1 induced HLH are rare in adults. We present the case and postmortem findings of a 27-year-old woman diagnosed with HLH in the setting of immunosuppression for the treatment of granulomatosis with polyangiitis (GPA). Autopsy revealed evidence of herpes simplex virus-1 (HSV-1) infection and no findings suggestive of GPA recurrence.

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Section: Discussionmentioning

confidence: 99%

“…Two of these patients recovered after receiving acyclovir, intravenous immunoglobulin, and etoposide or acyclovir alone and the third patient went on to require liver transplantation following acyclovir therapy. [9][10][11]…”

Section: Discussionmentioning

confidence: 99%

Herpes simplex virus-1 triggered hemophagocytic lymphohistiocytosis in a patient with granulomatosis with polyangiitis

States¹,

Kapp²

2022

Autops Case Rep

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“…HLH caused by HSV (HSV-HLH) has mainly been reported in infected neonates and is rare in adults. Following a search of the PubMed database, 11 case reports on adult patients with HSV-HLH were found in the English literature: 4 were caused by HSV-1 ( 6 , 10 - 12 ), 3 were caused by HSV-2 ( 13 - 15 ), and the others were caused by unspecified subtypes ( 16 - 19 ). The four previous adult cases of HSV-1-HLH and our case are summarized in Table 2 .…”

Section: Discussionmentioning

confidence: 99%

Successful Treatment of Herpes Simplex Virus (HSV)-1-associated Hemophagocytic Lymphohistiocytosis (HLH) with Acyclovir: A Case Report and Literature Review

et al. 2017

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Hemophagocytic lymphohistiocytosis (HLH) associated with herpes simplex virus (HSV)-1 infection (HSV-1-HLH) is uncommon and is potentially fatal without appropriate treatment. We herein report the case of an adult patient with HSV-1-HLH who was successfully treated with acyclovir. A 69-year-old man developed fever, pancytopenia and liver enzyme elevation after the resolution of pneumonia. These findings and the presence of hemophagocytosis in the patient's bone marrow were consistent with a diagnosis of HLH. The patient was diagnosed with HSV-1-HLH based on the results of a polymerase chain reaction (PCR) for HSV-1. The early administration of acyclovir improved his clinical symptoms and laboratory results within two weeks. In the present case, the rapid and precise diagnosis facilitated the successful treatment of HSV-1-HLH.

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“…Severe HSV-1 infections are mainly observed in immunosuppressed patients 3 who suffer from extensive, disseminated, or persistent herpetic lesions but also from more serious complications such as pneumonia 4 5 , encephalitis 6 7 , or hepatitis 8 9 . Thus, abundant and prolonged antiviral treatment is often inevitable but promotes the selection of resistant HSV-1 variants 3 .…”

mentioning

confidence: 99%

Recombinant herpes simplex virus type 1 strains with targeted mutations relevant for aciclovir susceptibility

Brunnemann

Liermann

Deinhardt‐Emmer

et al. 2016

Sci Rep

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Here, we describe a novel reliable method to assess the significance of individual mutations within the thymidine kinase (TK) gene of herpes simplex virus type 1 (HSV-1) to nucleoside analogue resistance. Eleven defined single nucleotide polymorphisms that occur in the TK gene of clinical HSV-1 isolates and a fluorescence reporter were introduced into the HSV-1 strain 17 + that had been cloned into a bacterial artificial chromosome. The susceptibility of these different strains to aciclovir, penciclovir, brivudin, and foscarnet was determined with a modified cytopathic effect reduction assay. The strains were also tested for their aciclovir susceptibility by measuring the relative fluorescence intensity as an indicator for HSV-1 replication and by quantifying the virus yield. Our data indicate that the amino acid substitutions R41H, R106H, A118V, L139V, K219T, S276R, L298R, S345P, and V348I represent natural polymorphisms of the TK protein, whereas G61A and P84L mediate broad cross-resistance against aciclovir, penciclovir, brivudin, and susceptibility to foscarnet. This method allows the definition of the resistance genotype of otherwise unclear mutations in the TK gene of HSV-1. Thus, it provides a scientific basis for antiviral testing in clinical isolates of patients suffering from serious diseases and will facilitate testing of new antivirals against HSV-1.Herpes simplex virus type 1 (HSV-1) belongs to the genus Simplexvirus of the Alphaherpesvirinae, a subfamily within the Herpesviridae 1 . With its high seroprevalence ranging in Europe from 50% to 90%, this human pathogen is of great medical importance 2 . After onset of primary infection, HSV-1 establishes a lifelong latency followed by endogenous reactivations 2 .Severe HSV-1 infections are mainly observed in immunosuppressed patients 3 who suffer from extensive, disseminated, or persistent herpetic lesions but also from more serious complications such as pneumonia 4,5 , encephalitis 6,7 , or hepatitis 8,9 . Thus, abundant and prolonged antiviral treatment is often inevitable but promotes the selection of resistant HSV-1 variants 3 . Approximately 2% to 10% of the immunosuppressed patients develop an infection or reactivation with HSV-1 variants resistant against antivirals in clinical use 10,11 . The highest rates of up to 45% have been described in patients who have received stem-cell transplantation 12 . So far, aciclovir (ACV) remains the drug of choice for prophylaxis and treatment of HSV infections 3 . Resistance-associated substitutions are predominantly observed within the viral thymidine kinase (TK) that otherwise converts the guanosine analogue to its active monophosphate form 13 . The incorporation of ACV results in DNA chain termination due to the missing hydroxyl group on the acyclic molecule. Accordingly, alterations of the TK-encoding gene UL23 are reported in 95% of clinical isolates resistant to ACV 14,15 . The high degree of UL23 sequence variability includes nucleotide deletions or insertions, which usually result in frame shifts or s...

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Persistent viral DNA detection in blood after primary herpes simplex 1 infection revealed by hepatitis with hemophagocytic syndrome

Cited by 7 publications

References 22 publications

Herpes simplex virus-1 triggered hemophagocytic lymphohistiocytosis in a patient with granulomatosis with polyangiitis

Herpes simplex virus-1 triggered hemophagocytic lymphohistiocytosis in a patient with granulomatosis with polyangiitis

Successful Treatment of Herpes Simplex Virus (HSV)-1-associated Hemophagocytic Lymphohistiocytosis (HLH) with Acyclovir: A Case Report and Literature Review

Recombinant herpes simplex virus type 1 strains with targeted mutations relevant for aciclovir susceptibility

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