Venezuelan equine encephalitis virus non-structural protein 3 (nsP3) interacts with RNA helicases DDX1 and DDX3 in infected cells.
The mosquito-borne New World alphavirus, Venezuelan equine encephalitis virus (VEEV) is a Category B select agent with no approved vaccines or therapies to treat infected humans. Therefore it is imperative to identify novel targets that can be targeted for effective therapeutic intervention. We aimed to identify and validate interactions of VEEV nonstructural protein 3 (nsP3) with host proteins and determine the consequences of these interactions to viral multiplication. We used a HA tagged nsP3 infectious clone (rTC-83-nsP3-HA) to identify and validate two RNA helicases: DDX1 and DDX3 that interacted with VEEV-nsP3. In addition, DDX1 and DDX3 knockdown resulted in a decrease in infectious viral titers. Furthermore, we propose a functional model where the nsP3:DDX3 complex interacts with the host translational machinery and is essential in the viral life cycle. This study will lead to future investigations in understanding the importance of VEEV-nsP3 to viral multiplication and apply the information for the discovery of novel host targets as therapeutic options.
National Center for Biodefense and Infectious Diseases, George Mason University, Manassas, VA, United States.
Moushimi
M
Amaya
National Center for Biodefense and Infectious Diseases, George Mason University, Manassas, VA, United States.
Taryn
T
Brooks-Faulconer
National Center for Biodefense and Infectious Diseases, George Mason University, Manassas, VA, United States.
Tyler
T
Lark
National Center for Biodefense and Infectious Diseases, George Mason University, Manassas, VA, United States.
Forrest
F
Keck
National Center for Biodefense and Infectious Diseases, George Mason University, Manassas, VA, United States.
Charles
C
Bailey
Johns Hopkins University, Departments of Radiology and Oncology, Maryland, United States.
Venu
V
Raman
National Center for Biodefense and Infectious Diseases, George Mason University, Manassas, VA, United States. Electronic address: anaraya1@gmu.edu.
Aarthi
A
Narayanan
D000818:Animals; D002460:Cell Line; D002522:Chlorocebus aethiops; D053487:DEAD-box RNA Helicases / Q000172:deficiency / Q000235:genetics / Q000378:metabolism*; D004666:Encephalitis Virus, Venezuelan Equine / Q000737:chemistry / Q000378:metabolism*; D055785:Gene Knockdown Techniques; D054884:Host-Pathogen Interactions; D006801:Humans; D020365:RNA Helicases / Q000378:metabolism; D014709:Vero Cells; D019562:Viral Load; D017361:Viral Nonstructural Proteins / Q000378:metabolism*; D014779:Virus Replication
D017361:Viral Nonstructural Proteins; C089383:nsp3 protein, alphavirus; C086252:DDX1 protein, human; C119332:DDX3X protein, human; D053487:DEAD-box RNA Helicases; D020365:RNA Helicases