Two avirulent herpes simplex viruses generate lethal recombinants in vivo

Area of Science:

• Virology
• Molecular Biology
• Immunology

Background:

• Virulent viruses cause disease, but the pathogenic potential of avirulent virus mixtures via complementation or recombination in vivo is not well-established.
• Herpes simplex virus type 1 (HSV-1) is a common human pathogen with various strains exhibiting different virulence levels.

Purpose of the Study:

• To investigate if a mixture of avirulent herpes simplex virus type 1 (HSV-1) strains can cause lethal disease through in vivo genetic interactions.
• To determine if recombination between weakly neuroinvasive HSV-1 strains can generate virulent progeny.

Main Methods:

• Simultaneous inoculation of two weakly neuroinvasive HSV-1 strains (ANG and KOS) onto the footpads of mice.
• Monitoring animal survival rates after inoculation with virus mixtures or individual strains.
• Isolation and characterization of viruses from the brains of deceased mice, including genetic analysis of progeny viruses.

Main Results:

• Mice inoculated with a 1:1 mixture of two weakly neuroinvasive HSV-1 strains exhibited a high mortality rate (62%).
• Mice inoculated with equivalent or higher doses of either individual HSV-1 strain survived.
• Eleven of fourteen viruses isolated from deceased mice were recombinant, and three of these recombinants were lethal upon re-inoculation.

Conclusions:

• Avirulent HSV-1 strains can interact in vivo to produce virulent recombinants, leading to lethal infections.
• The study provides evidence for genetic complementation and recombination as mechanisms for generating virulence in viruses.
• Different genetic lesions likely contribute to the attenuated neuroinvasiveness of the HSV-1 strains ANG and KOS.