CMPK2 Restricts the Replication of Multiple Flaviviruses

C.E. Credits: P.A.C.E. CE Florida CE
Speaker

Abstract

Flaviviruses are pathogens of global public health concern. They include dengue virus (DENV), West Nile virus (WNV), and zika virus (ZIKV). There are no approved US Food and Drug Administration antivirals for any flavivirus. The type I interferon (IFN-I) system is the first line of defense against viral infection. Activation of IFN-I signaling leads to the induction of hundreds of IFN stimulated genes (ISGs), the products of many serve to limit viral replication. One of these ISGs, Cytidine monophosphate kinase (CMPK2), is a potential anti-flavivirus drug target. CMPK2 is an interferon inducible enzyme with a mitochondrial localization sequence (MLS) at its N-terminus that localizes it to the mitochondria where it plays an important role in maintenance of cellular nucleic acid synthesis. The N-terminal domain (NTD) of human CMPK2 contains no known sequence homology to any other species and the C-terminal domain (CTD) is highly conserved across species and is responsible for its kinase activity. CMPK2 was reported to inhibit human immunodeficiency virus (HIV) and DENV replication. However, the molecular mechanism by which CMPK2 restricts these viruses is unclear. Here we show that expression of CMPK2 inhibits the replication of multiple flaviviruses including ZIKV.  We show that the mitochondrial localization of CMPK2 is required for its antiviral activity. Moreover, we show that the NTD of CMPK2 is sufficient for its antiviral activity thus the kinase activity is not required for CMPK2 antiviral function. Future studies will focus on the molecular mechanisms by which CMPK2 inhibits flavivirus replication. This knowledge will aid in the design of novel therapeutic antiviral strategies.


Learning objectives:
1. Identify CMPK2 as a host restriction factor for multiple flaviviruses.
2. To explain that the mitochondrial localization of CMPK2 is required for its antiviral function, and its kinase function is dispensable. 


Show Resources
You May Also Like
SEP 14, 2021 7:00 AM PDT
C.E. CREDITS
SEP 14, 2021 7:00 AM PDT
Date: September 14, 2021 Time: 7am PDT, 10am EDT, 4pm CEST A conventional thermal cycler has long been a commodity product in the lab and end-point PCR techniques can be completed almost wit...
NOV 09, 2021 11:00 AM PST
C.E. CREDITS
NOV 09, 2021 11:00 AM PST
Date: November 09, 2021 Time: 11:00am (PDT), 02:00pm (EDT) Clinical translation of human pluripotent stem cells (hPSCs) requires advanced strategies that ensure safe and robust long-term gro...
SEP 17, 2021 12:00 PM CST
C.E. CREDITS
SEP 17, 2021 12:00 PM CST
Date: September 16, 2021 Time: 9:00pm (PDT), 12:00am (EDT) 3D cellular models like organoids and spheroids offer an opportunity to better understand complex biology in a physiologically rele...
OCT 20, 2021 10:00 AM PDT
C.E. CREDITS
OCT 20, 2021 10:00 AM PDT
Date: October 20, 2021 Time:10:00am (PDT), 1:00pm (EDT) As the prevalence of Diabetes continues to rise in many areas across the globe, healthcare providers continue to look for methods that...
NOV 30, 2021 10:00 AM PST
C.E. CREDITS
NOV 30, 2021 10:00 AM PST
Date: November 30, 2021 Time: 10:00am (PDT), 1:00pm (EDT) The prevalence of thyroid disease worldwide has served as a catalyst for healthcare providers to study various tools and methods to...
JAN 13, 2022 9:00 AM PST
C.E. CREDITS
JAN 13, 2022 9:00 AM PST
Date: January 13, 2022 Time: 09:00am (PST), 12:00pm (EST) Recently, the Infectious Disease Society of America released guidance on how to approach treatment of infections caused by multidrug...
Loading Comments...
Show Resources