Title : Viral proteins activating PKA as an antiviral vaccine target

Viral infections like HIV and Ebola have created a link to the intracellular stress system via the cAMP-PKA pathway. This allows the virus to suppress T-helper cell activation and interferon signaling, while simultaneously using PKA to boost its replication in the case of Ebola infection. Cells of the immune system decrease in size and can’t fulfill their tasks anymore, for example in HIV the central part of inactivation of the immune system is suppression of T-helper cells and an arrest of the cell cycle. The Ebola virus seems to be even more proficient in finding ways to weaken various cell systems, for example endothelial cells. It debilitates interferon signaling more intensely than in the case of HIV by additionally blocking downstream interferon signaling, which is equally linked to and inactivated by PKA activation. The cAMP-PKA pathway is mediating an ongoing stress response via beta-receptors, stress is basically creating an increased activity of PKA in immune cells and therefore a reduced capacity to respond to infections similar to what certain viruses do to immune cells. Certain non-selective beta blockers reduce this inactivation and lead to an increased capacity to process viral infections.

Background: Former research included the impact of propranolol on the stress-related cAMP-PKA pathway in cells of the immune system, which has laid the ground for further exploration of its influence on viral infections. Propranolol may even be used as an adjuvant in vaccines.

Methods: Review of available publications.

Results: The impact of some viral infections like Ebola and HIV on cells of the immune system is mediated initially by viral proteins that bind to and activate PKA which incapacitates immune cells functionally. PKA activation mediates the inhibition of interferon signaling, cell cycle arrest, and other functions of the immune system.

Conclusions: For vaccine development the viral proteins connecting to PKA may be good candidates for mRNA or possibly peptide vaccines, for example the VP35 protein of the Ebola virus. For HIV the proteins connecting to PKA are viral protein R (Vpr), capsid (p24), nef (negative factor) and vif (viral infec-tivity factor).

Karin E. Peuschel studied medicine and molecular biology at the University of Zurich (Switzerland), she completed her medical thesis from the University of Zurich in the field of ophthalmology. She worked in prion research in Zurich Switzerland and has published some of her findings. She discovered the antiviral activity of propranolol. She is currently the director of Dr. med. Karin Peuschel in Zug (Switzerland) and researcher in psychiatry and psychotherapy. She has published papers and has been active as a speaker in the fields of molecular biology, infectious diseases and pharmacology, as well as in psychiatry and psychotherapy and has been serving as a reviewer and an organizing committee member.