Dengue Virus Non-Structural Protein 5 as a Versatile, Multi-Functional Effector in Host–Pathogen Interactions

Frontiers in Cellular and Infection Microbiology

Ramakrishnan Sitaraman¹  Priya Bhatnagar²  Gopinathan Pillai Sreekanth³  Anmol Chandele³  Kaja Murali-Krishna⁴ 

[1] Department of Biotechnology, TERI School of Advanced Studies, New Delhi, India;Department of Biotechnology, TERI School of Advanced Studies, New Delhi, India;ICGEB-Emory Vaccine Centre, International Centre for Genetic Engineering and Biotechnology (ICGEB), New Delhi, India;ICGEB-Emory Vaccine Centre, International Centre for Genetic Engineering and Biotechnology (ICGEB), New Delhi, India;ICGEB-Emory Vaccine Centre, International Centre for Genetic Engineering and Biotechnology (ICGEB), New Delhi, India;Department of Paediatrics and Emory Vaccine Centre, Emory University School of Medicine, Atlanta, GA, United States;

关键词: Flavivirus;    NS5;    moonlighting proteins;    signaling pathways;    protein–protein interactions (PPIs);    antiviral immunity;    apoptosis;    spliceosome;   

DOI  :  10.3389/fcimb.2021.574067

来源: Frontiers

【 摘 要 】

Dengue is emerging as one of the most prevalent mosquito-borne viral diseases of humans. The 11kb RNA genome of the dengue virus encodes three structural proteins (envelope, pre-membrane, capsid) and seven non-structural proteins (NS1, NS2A, NS2B, NS3, NS4A, NS4B, and NS5), all of which are translated as a single polyprotein that is subsequently cleaved by viral and host cellular proteases at specific sites. Non-structural protein 5 (NS5) is the largest of the non-structural proteins, functioning as both an RNA-dependent RNA polymerase (RdRp) that replicates the viral RNA and an RNA methyltransferase enzyme (MTase) that protects the viral genome by RNA capping, facilitating polyprotein translation. Within the human host, NS5 interacts with several proteins such as those in the JAK-STAT pathway, thereby interfering with anti-viral interferon signalling. This mini-review presents annotated, consolidated lists of known and potential NS5 interactors in the human host as determined by experimental and computational approaches respectively. The most significant protein interactors and the biological pathways they participate in are also highlighted and their implications discussed, along with the specific serotype of dengue virus as appropriate. This information can potentially stimulate and inform further research efforts towards providing an integrative understanding of the mechanisms by which NS5 manipulates the human-virus interface in general and the innate and adaptive immune responses in particular.

【 授权许可】

CC BY