Non-cytopathic herpes simplex virus type-1 isolated from acyclovir-treated patients with recurrent infections

Autor: Subrata Roy, Soumi Sukla, Abhishek De, Subhajit Biswas
Jazyk: angličtina
Rok vydání: 2022
Předmět:
Zdroj: Scientific Reports, Vol 12, Iss 1, Pp 1-15 (2022)
Druh dokumentu: article
ISSN: 2045-2322
DOI: 10.1038/s41598-022-05188-w
Popis: Abstract Herpes simplex virus (HSV) usually produces cytopathic effect (CPE) within 24-72 h post-infection (P.I.). Clinical isolates from recurrent HSV infections in patients on Acyclovir therapy were collected between 2016 and 2019 and tested in cell cultures for cytopathic effects and further in-depth characterization. Fourteen such isolates did not show any CPE in A549 or Vero cell lines even at 120 h P.I. However, these cultures remained positive for HSV-DNA after several passages. Sequence analysis revealed that the non-CPE isolates were all HSV-1. Analysis of the thymidine kinase gene from the isolates revealed several previously reported and two novel ACV-resistant mutations. Immunofluorescence and Western blot data revealed a low-level expression of the immediate early protein, ICP4. Late proteins like ICP5 or capsid protein, VP16 were almost undetectable in these isolates. AFM imaging revealed that the non-CPE viruses had structural deformities compared to wild-type HSV-1. Our findings suggest that these strains are manifesting an unusual phenomenon of being non-CPE herpesviruses with low level of virus protein expressions over several passages. Probably these HSV-1 isolates are evolving towards a more “cryptic” form to establish chronic infection in the host thereby unraveling yet another strategy of herpesviruses to evade the host immune system.
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