Equid herpes simplex viruses 1 and 4 encode functional homologs of the herpes simplex virus type 1 virion transactivator protein, VP16.

The herpes simplex virus type 1 (HSV-1) tegument protein VP16 is a potent transcriptional inducer of immediate-early gene expression, comprising an N-terminal domain involved in binding DNA linked to an acidic transactivating C-terminal domain. The gene encoding the counterpart of this protein in equid herpes simplex virus 4 (EHV-4) was sequenced. Comparisons with VP16 and the homologous proteins of equine herpes simplex virus 1 (EHV-1) and varicella-zoster virus (VZV) showed that a region in the N-terminal domain involved in formation of a complex with cellular proteins is partially conserved in all four proteins. In contrast, the C-terminal regions of the EHV proteins, like that of VZV, are not particularly acidic and are not significantly conserved with respect to the C-terminal region of VP16. Nevertheless, transient expression experiments indicated that the EHV-1 and EHV-4 proteins are able to transactivate HSV-1 and EHV-1 immediate-early promoters in a dose-dependent manner, which suggests that this activity is not dependent on an acidic C-terminal domain.

Otarine herpes simplex virus-1: a novel gammaherpes virus associated with urogenital carcinoma in California sea lions (Zalophus californianus).

The incidence of neoplasia in California sea lions (CSLs) is considered to be unusually high. Electron microscopic examination of some of these urogenital tumours revealed the presence of virions with typical herpes-like structure. While current attempts to cultivate this virus have not been successful, molecular studies employing DNA extracted from tumour tissues allowed both the classification of the agent and its identification in tumours and archived tissue samples. Two genome fragments generated using degenerate primers in PCR demonstrated highest identities with other mammalian gammaherpes viruses. Phylogenetic analysis showed that this novel virus, tentatively designated Otarine herpes simplex virus-1 (OtHV-1), grouped with members of the gammaherpes virus subfamily and was distinct from PHV-2, a previously described pinniped gammaherpes virus. An OtHV-1 specific PCR was established and used to investigate the presence of this virus in CSL tissues. PCR of DNA isolated from animals with these tumours, demonstrated that this virus was present in 100% (16/16) of tumours. Furthermore, DNA extracted from archived brain and muscle tissues was also positive in 29% (4/14) and 50% (7/14) of cases examined. This preliminary study provides evidence to support the hypothesis that the presence of this novel gammaherpes virus is a factor in the development of urogenital carcinoma in CSLs.

Detection of cervical infections in colposcopy clinic patients.

The purpose of this study was to determine if Neisseria gonorrhoeae; Chlamydia trachomatis; herpes simplex virus; cytomegalovirus; Epstein-Barr virus; human herpes simplex viruses 6, 7, and 8; or adeno-associated virus influenced the production of cervical intraepithelial neoplasia. Two hundred thirty-one cervical smear samples were tested for the presence of the organisms by PCR. In addition, human papillomavirus types in the samples were determined by PCR and classified into cancer risk types of high, moderate, and low. There was no link with cervical intraepithelial neoplasia status and detection of herpes simplex virus, cytomegalovirus, Epstein-Barr virus, human herpes simplex viruses 6 and 8, gonorrhea, or chlamydia. However, high-grade cervical intraepithelial neoplasia was found more frequently with mixed infection by moderate-risk human papillomavirus types and human herpes simplex virus 7 than with these papillomavirus types alone. The presence of human herpes simplex virus 7 may increase the oncogenic potential of moderate-risk human papillomavirus types.

Glycoprotein gD of MDV lacks functions typical for alpha-herpes virus gD homologues.

Glycoprotein D (gD) belongs to family of conserved structural proteins of alpha-herpes viruses. During productive infection of cells by herpes simplex virus 1 (HSV-1) gD has several important functions, is involved in virus penetration to and release from infected cells and is one of main targets of neutralizing antibodies. Similar functions are shared also by other alpha-herpes virus gD homologues. Surprisingly, in previous studies it was found that MDV gD expression could not be detected during infection in vitro using immunological methods. In this study we have analyzed expression of MDV gD and its biological consequences. In vitro expression using rabbit reticulocyte lysate and/or overexpression in transfected cells showed that the second ATG codon is required for synthesis of mature, glycosylated gD. In addition, it was found that gD overexpression is neither toxic for transfected cells nor is involved in membrane fusion. After MDV infection of a proprietary cell line stably transfected with plasmid overexpressing MDV gD, no viral particles could be found in culture. On the other hand, cells overexpressing the MDV gD were sensitive to MDV infection in similar way as parental, non-transfected cells. From our study and results of other authors we propound the following conclusions: (i) MDV gD expression is blocked during in vitro infection at transcription level; (ii) MDV gD is lacking many important functions characteristic for other alpha-herpes virus gD homologues; (iii) overexpression of single MDV gD does not result in production of mature infectious MDV particles.