Herpes simplex virus induces the replication of foreign DNA

Area of Science:

• Virology
• Molecular Biology
• Genetics

Background:

• Simian virus 40 (SV40) DNA replication origins and large T antigen enable efficient plasmid replication in Vero monkey cells.
• SV40-based plasmids do not replicate efficiently in rabbit skin cells without specific viral intervention.

Purpose of the Study:

• To investigate the ability of herpes simplex virus (HSV) to induce replication of foreign DNA in non-permissive cells.
• To elucidate the mechanisms and requirements of HSV-mediated DNA replication.

Main Methods:

• Transfection of rabbit skin cells with plasmids containing SV40 replication origins and large T gene.
• Infection of transfected cells with HSV-1 and HSV-2.
• Analysis of plasmid replication, DNAconcatemers, and sensitivity to phosphonoacetate.
• Testing replication of plasmids lacking known eukaryotic origins.

Main Results:

• HSV-1 and HSV-2 infection enabled efficient replication of SV40-based plasmids in rabbit skin cells.
• HSV-induced replication required the large T antigen and SV40 origin but produced HSV-like concatemers.
• Replication was sensitive to phosphonoacetate, indicating involvement of HSV DNA polymerase or related viral products.
• HSV also induced low-level replication of plasmids lacking known origins.

Conclusions:

• Herpes simplex virus induces a DNA replicative activity capable of amplifying foreign DNA in host cells.
• The mechanism involves HSV DNA polymerase or other viral gene products expressed during HSV replication.
• These findings suggest a potential role for HSV in the transformation of cells through foreign DNA amplification.