Replication at body temperature selects a neurovirulent herpes simplex virus type 2

Area of Science:

• Virology
• Infectious Diseases
• Neuroscience

Background:

• Herpes simplex virus type 2 (HSV-2) is a significant human pathogen.
• Understanding viral adaptation and virulence is crucial for disease control.
• Temperature sensitivity can influence viral pathogenicity.

Purpose of the Study:

• To investigate the adaptation and virulence of a prototype HSV-2 strain (HG-52) at different temperatures.
• To determine if serial passage at a higher temperature (37.5°C) affects the avirulent nature of HSV-2 (HG-52) at a lower temperature (31°C).
• To elucidate the mechanisms underlying viral virulence selection.

Main Methods:

• A prototype HSV-2 strain (HG-52) was serially passaged in mice at 31°C and 37.5°C.
• Avirulence and virulence were assessed by intracranial inoculation in mice.
• Viral replication capacity in the brain was evaluated.
• Plaque purification was used to isolate viral descendants.

Main Results:

• HSV-2 (HG-52) replicated at 31°C was avirulent in mice upon intracranial inoculation.
• Serial passage at 31°C did not alter the avirulence of the virus.
• Passage at 37.5°C resulted in a virulent viral population.
• The selection favored viruses with enhanced replication capacity in the mouse brain, not just higher replication at 37.5°C.
• Virulent variants were successfully derived from plaque-purified avirulent stocks.

Conclusions:

• Temperature adaptation significantly influences HSV-2 virulence.
• Selection at a physiologically relevant temperature (37.5°C) can rapidly generate virulent HSV-2 strains from avirulent precursors.
• Enhanced neurovirulence is associated with increased replication capacity within the host brain.
• These findings have implications for understanding HSV-2 pathogenesis and evolution.