Herpes simplex virus types 1 and 2 completely help adenovirus-associated virus replication

Area of Science:

• Virology
• Molecular Biology
• Cellular Biology

Background:

• Adenovirus-associated virus (AAV) requires helper virus activity for replication.
• Herpesviruses were previously thought to provide only partial AAV helper activity.
• Adenoviruses are known complete helpers for AAV multiplication.

Purpose of the Study:

• To investigate the helper activity of herpes simplex virus type 1 (HSV-1) and type 2 (HSV-2) on AAV replication.
• To determine if HSV-1 and HSV-2 can act as complete helpers for AAV, enabling infectious particle assembly.

Main Methods:

• Coinfection experiments were performed using HSV-1 and HSV-2 strains with AAV type 2 (AAV2) in various cell lines (KB, HeLa, HEp-2, human embryonic kidney cells).
• AAV helper activity was assessed by measuring AAV DNA, RNA, and protein synthesis and infectious particle yields.
• Time course analyses compared AAV2 macromolecular synthesis rates in cells coinfected with adenovirus type 5 versus HSV-1.

Main Results:

• HSV-1 and HSV-2 demonstrated complete AAV helper activity, supporting AAV2 infectivity yields comparable to those with adenovirus helpers.
• AAV2 multiplication was efficient in KB and HeLa cells coinfected with HSV strains.
• HSV-1 also supported AAV1 multiplication, though less efficiently than AAV2, and accelerated AAV2 macromolecular synthesis compared to adenovirus.

Conclusions:

• Herpes simplex viruses (HSV-1 and HSV-2) function as complete helpers for AAV replication, a finding that expands our understanding of AAV-helper virus interactions.
• The temporal dynamics of AAV macromolecular synthesis are linked to the helper virus replication cycle.
• These results challenge the previous notion of partial helper activity for herpesviruses in AAV replication.