Neonatal HSV is most commonly transmitted at the time of delivery with the risk being dramatically higher if the mother has first-episode genital HSV and does not have an elective Cesarean section. Maternal HSV type-specific serology can be used to differentiate first-episode from recurrent infection in this setting, allowing for use of empiric acyclovir for the highest risk infants. There is a need for new strategies as current methods of prevention of transmission of HSV to neonates have limited effectiveness, as they do not account for the fact that the majority of transmission occurs from asymptomatic women. After transmission has occurred, early recognition of neonatal HSV improves the prognosis. Diagnosis needs to be considered in all infants who develop vesicles, unexplained seizures, or possible sepsis in the first 5 weeks of life.
[Show abstract][Hide abstract] ABSTRACT: A late preterm neonate born by cesarean section with intact membranes presented at 9 days of life with shock and liver failure. Surface cultures were negative but whole blood polymerase chain reaction was positive for herpes simplex virus type 2, underscoring the value of this test in early diagnosis of perinatally acquired disseminated herpes simplex virus infection without skin lesions.
[Show abstract][Hide abstract] ABSTRACT: Herpes simplex virus type 1 (HSV-1), a member of the herpesviridae, causes a variety of human viral diseases globally. Although a series of antiviral drugs are available for the treatment of infection and suppression of dissemination, HSV-1 remains highly prevalent worldwide. Therefore, the development of novel antiviral agents with different mechanisms of action is a matter of extreme urgency. During the proliferation of HSV-1, capsid assembly is essential for viral growth, and it is highly conserved in all HSV-1 strains. In this study, small interfering RNAs (siRNAs) against the HSV-1 capsid protein were screened to explore the influence of silencing capsid expression on the replication of HSV-1. We designed and chemically synthesized siRNAs for the capsid gene and assessed their inhibitory effects on the expression of target mRNA and the total intracellular viral genome loads by quantitative real-time PCR, as well as on the replication of HSV-1 via plaque reduction assays and electron microscopy. Our results showed that siRNA was an effective approach to inhibit the expression of capsid protein encoding genes including UL18, UL19, UL26, UL26.5, UL35 and UL38 in vitro. Interference of capsid proteins VP23 (UL18) and VP5 (UL19) individually or jointly greatly affected the replication of clinically isolated acyclovir-resistant HSV-1 as well as HSV-1/F and HSV-2/333. Plaque numbers and intracellular virions were significantly reduced by simultaneous knockdown of UL18 and UL19. The total intracellular viral genome loads were also significantly decreased in the UL18 and UL19 knockdown groups compared with the viral control. In conclusion, interfering with UL18 and UL19 gene expression could inhibit HSV-1 replication efficiently in vitro. Our research offers new targets for an RNA interference-based therapeutic strategy against HSV-1.
PLoS ONE 05/2014; 9(5):e96623. DOI:10.1371/journal.pone.0096623 · 3.23 Impact Factor
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