No abstract

Herpes simplex virus type 1 (HSV-1) and varicella zoster virus (VZV) are closely related viruses causing lifelong infections. They are typically associated with mucocutaneous or skin lesions, but may also cause severe neurological or ophthalmic diseases, possibly due to viral- and/or host-genetic factors. Although these viruses are well characterized, genome-wide evolutionary studies have hitherto only been presented for VZV. Here, we present a genome-wide study on HSV-1. We also compared the evolutionary characteristics of HSV-1 with those for VZV. We demonstrate that, in contrast to VZV for which only a few ancient recombination events have been suggested, all HSV-1 genomes contain mosaic patterns of segments with different evolutionary origins. Thus, recombination seems to occur extremely frequent for HSV-1. We conclude by proposing a timescale for HSV-1 evolution, and by discussing putative underlying mechanisms for why these otherwise biologically similar viruses have such striking evolutionary differences.

An immunoblot assay for discrimination of antibodies to herpes simplex virus (HSV) types 1 and 2 was devised using extracts of recombinant-baculovirus-infected insect cells expressing HSV-1 or -2 glycoprotein G (gG1 or gG2). The assay was evaluated by comparing its results with those obtained by using an immunodot assay based on gG immunopurified from HSV-1- and HSV-2-infected cells. Each of 110 human serum specimens was tested blindly and independently three times. At a serum dilution of 1:20, the maximum specificities were 96% and 100% and the maximum sensitivities were 100% and 92% for gG1 and gG2, respectively. Reproducibility was 99% among readers and 95% among individually tested samples of each specimen. Results obtained in two laboratories from a different set of 15 serum specimens were in complete agreement, indicating the assay is accurate and reproducible. The ease of antigen production should allow the test to become widely available.

The character of diseases caused by alphaherpesviruses has changed over the last decade. The severity of disease and the frequency of acyclovir resistance has increased with the increase in the number of immunocompromised patients. Compounding the trend towards more virulent herpes disease is the current emphasis towards outpatient management of many diseases. Much of the current antiviral research focuses on providing drugs with (i) improved oral bioavailability and pharmacokinetics which permit less frequent oral or topical dosing for suppressive treatment of herpes simplex virus (HSV) infections, (ii) different mechanisms of action for synergic effects in treating resistant HSV infections in the immunocompromised host and (iii) improved efficacy. Future antiviral agents will probably target enzymes or viral factors essential for infection or will inhibit other steps in the viral infection cycle, such as viral entry, protein synthesis or capsid assembly. Medications that augment the immune response constitute another pathway for combating herpes viral infections. Many of the newer experimental agents target essential processes unique to herpesvirus replication and, therefore, potentially have high selectivity.

The herpes simplex virus (HSV) recombinant virus R7020 is an attenuated virus designed as a candidate for immunization against both HSV-1 and HSV-2 infections. It was extensively tested in an experimental animal system and in a healthy human adult population without significant untoward effects. We report on the use of R7020 with ionizing radiation as an oncolytic agent for hepatomas. Two hepatoma cell lines were studied, Hep3B and Huh7. R7020 replicated to higher titers in Hep3B cells than in Huh7 cells. Tissue culture studies correlated with hepatoma xenograft responses to R7020. R7020 was more effective in mediating Hep3B tumor xenograft regression compared with Huh7. Ionizing radiation combined with R7020 also showed differential results in antitumor efficacy between the two cell lines in tumor xenografts. Ionizing radiation enhanced the replication of R7020 in Hep3B xenografts. Moreover, the combination of ionizing radiation and virus caused a greater regression of xenograft volume than either R7020 or radiation alone. Ionizing radiation had no effect on the replication of R7020 virus in Huh7 xenografts. These results indicate that a regimen involving infection with an appropriate herpesvirus such as R7020 in combination with ionizing radiation can be highly effective in eradicating certain tumor xenografts.