Alterations in the cellular phenotype induced by herpes simplex viruses

Area of Science:

• Virology
• Oncology
• Molecular Biology

Background:

• Herpes simplex virus types 1 and 2 (HSV-1, HSV-2) are known to induce morphological transformation in rodent cells.
• Unlike other DNA tumor viruses, HSV-transformed cells do not consistently retain viral genes, challenging traditional oncogenic models.

Purpose of the Study:

• To investigate the mechanisms by which HSV induces cellular transformation.
• To explore the potential role of HSV in multistage oncogenic transformation, particularly in the context of human anogenital tumors.

Main Methods:

• Analysis of viral DNA fragments capable of inducing transformation.
• Investigation of HSV's ability to induce mutations, gene rearrangements, and gene amplification.
• Assessment of HSV's effects on endogenous retroviral expression and host cell gene transcription.

Main Results:

• HSV transformation can occur using viral DNA fragments lacking complete viral protein-coding sequences.
• HSV is capable of inducing point mutations, gene rearrangements, and gene amplification.
• HSV can activate endogenous retroviruses and alter host cell gene expression, suggesting a broader role in cellular changes.

Conclusions:

• The "hit-and-run" hypothesis is supported by the observation that HSV can transform cells without persistent viral DNA.
• HSV's ability to induce genetic instability and alter cellular gene expression suggests its involvement in a multistage process of oncogenic transformation.
• The findings are consistent with the difficulty in detecting HSV DNA in human tumors and imply a potential role for HSV in neoplasia etiology.