Experimental Dissection of the Lytic Replication Cycles of Herpes Simplex Viruses in vitro

Abstract

Herpes simplex viruses type 1 and type 2 (HSV-1 and HSV-2) produce lifelong infections and are highly prevalent in the human population. Both viruses elicit numerous clinical manifestations and produce mild-to-severe diseases that affect the skin, eyes, and brain, among others. Despite the existence of numerous antivirals against HSV, such as acyclovir and acyclovir-related analogs, virus variants that are resistant to these compounds can be isolated from immunosuppressed individuals. For such isolates, second-line drugs can be used, yet they frequently produce adverse side effects. Furthermore, topical antivirals for treating cutaneous HSV infections usually display poor to moderate efficacy. Hence, better or novel anti-HSV antivirals are needed and details on their mechanisms of action would be insightful for improving their efficacy and identifying specific molecular targets. Here, we review and dissect the lytic replication cycles of herpes simplex viruses, discussing key steps involved in cell infection and the processes that yield new virions. Additionally, we review and discuss rapid, easy-to-perform and simple experimental approaches for studying key steps involved in HSV replication to facilitate the identification of the mechanisms of action of anti-HSV compounds.

RNA Polymerase II Promoter-Proximal Pausing and Release to Elongation Are Key Steps Regulating Herpes Simplex Virus 1 Transcription

“…2 and 3). It is well known and documented that the expression levels of late genes do not peak until much later during infection (17,26,44,45). These observations suggest that recruitment of Pol II to ␥ gene promoters through the activities of HSV-1 ␣ gene products cannot fully account for the robust transcription of late genes after 6 hpi (Fig.…”

“…This comparison required temporal assignment of genes. For 31 genes, the temporal designations were agreed upon in multiple reports (7,17,24,26,28,44,66). When the remaining genes were examined for temporal class designation, we noted that many of the genes that were designated ␥ 1 or ␥ 2 genes by immunoblotting were designated ␤ genes by transcriptional analysis through either microarray or Northern blot experiments (26,28,44,45,66).…”

Antiviral effect of Chinese herbal prescription JieZe-1 on adhesion and penetration of VK2/E6E7 with herpes simplex viruses type 2

“…Firstly, we explored the anti-HSV-2 effects of JZ-1, penciclovir and berberine at 6 h, 12 h, 18 h, and 24 h of treatment. Immunofluorescence microscopy analysis of gD expression showed that only JZ-1 had an antiviral effect at the treatment of 6 h. Since the late gene transcription products of HSV-2, including gB, gC, gD, gE, gG, and other viral structural proteins, are produced significantly 12-15 h after infection (Ibáñez et al, 2018;Su et al, 2017), the gD observed in host cells at 6 h of infection was mostly derived from the original virons that infected the cells, suggesting that JZ-1 plays a vital role in the early Fig. 5.…”

Anti-herpetic Activity of Macrocystis pyrifera and Durvillaea antarctica Algae Extracts Against HSV-1 and HSV-2

“…To assess the possibility that the algae extracts block the ability of the viruses to bind to the cell surface, we evaluated the amount of HSV particles bound to the surface of HeLa cells inoculated with the viruses at 4°C, by determining the amount of glycoprotein B and glycoprotein D present in the cells after an incubation period of 5 h at this temperature ( Ibáñez et al, 2018 ). As shown in Figure 6A , the treatment with the M. pyrifera extract decreased the amount of HSV-2 bound to the cell surface.…”