Generation and Characterization of UL21-Null Herpes Simplex Virus Type 1

Area of Science:

• Virology
• Molecular Biology
• Cell Biology

Background:

• Herpes simplex virus type 1 (HSV-1) UL21 is an accessory protein involved in the viral tegument.
• The precise functions of UL21 and its homologs across different herpesvirus subfamilies remain largely undefined.

Purpose of the Study:

• To elucidate the role of the HSV-1 UL21 protein in viral replication and cellular interactions.
• To investigate the impact of UL21 deficiency on HSV-1 growth kinetics and virion assembly.

Main Methods:

• Generation of a UL21-null HSV-1 mutant.
• Comparative growth analysis of wild-type and UL21-null HSV-1 in glial cells.
• Yeast two-hybrid screening to identify UL21-interacting proteins.
• Immunofluorescence microscopy to assess GFAP distribution in infected cells.

Main Results:

• UL21-null HSV-1 exhibited delayed synthesis of infectious virions and reduced overall yield in glial cells.
• Plaque formation was significantly smaller for the UL21-null mutant compared to wild-type HSV-1.
• Yeast two-hybrid screening identified intermediate filaments, including GFAP, as potential UL21 interactors.
• Altered GFAP distribution was observed in glial cells infected with the UL21-null mutant.

Conclusions:

• HSV-1 UL21 protein plays a significant role in promoting efficient viral replication and infectious virion production in glial cells.
• UL21 may influence viral assembly or egress by interacting with host cell intermediate filaments, specifically GFAP.
• These findings contribute to a better understanding of HSV-1 pathogenesis and the function of tegument proteins.