The Putative Roles and Functions of Indel, Repetition and Duplication Events in Alphavirus Non-Structural Protein 3 Hypervariable Domain (nsP3 HVD) in Evolution, Viability and Re-Emergence
Nurshariza Abdullah,
Nafees Ahemad,
Konstantinos Aliazis,
Jasmine Elanie Khairat,
Thong Chuan Lee,
Siti Aisyah Abdul Ahmad,
Nur Amelia Azreen Adnan,
Nur Omar Macha,
Sharifah Syed Hassan
Affiliations
Nurshariza Abdullah
Jeffrey Cheah School of Medicine and Health Sciences, Monash University Malaysia, Bandar Sunway 47500, Selangor, Malaysia
Nafees Ahemad
School of Pharmacy, Monash University Malaysia, Bandar Sunway 47500, Selangor, Malaysia
Konstantinos Aliazis
Institute of Immunology and Immunotherapy, Centre for Liver and Gastrointestinal Research, University of Birmingham, Birmingham B15 2TT, UK
Jasmine Elanie Khairat
Institute of Biological Sciences, Faculty of Science, University Malaya, Kuala Lumpur 50603, Malaysia
Thong Chuan Lee
Faculty of Industrial Sciences & Technology, University Malaysia Pahang, Lebuhraya Tun Razak, Gambang, Kuantan 26300, Pahang, Malaysia
Siti Aisyah Abdul Ahmad
Immunogenetic Unit, Allergy and Immunology Research Center, Institute for Medical Research, Ministry of Health Malaysia, Shah Alam 40170, Selangor, Malaysia
Nur Amelia Azreen Adnan
Jeffrey Cheah School of Medicine and Health Sciences, Monash University Malaysia, Bandar Sunway 47500, Selangor, Malaysia
Nur Omar Macha
Jeffrey Cheah School of Medicine and Health Sciences, Monash University Malaysia, Bandar Sunway 47500, Selangor, Malaysia
Sharifah Syed Hassan
Jeffrey Cheah School of Medicine and Health Sciences, Monash University Malaysia, Bandar Sunway 47500, Selangor, Malaysia
Alphavirus non-structural proteins 1–4 (nsP1, nsP2, nsP3, and nsP4) are known to be crucial for alphavirus RNA replication and translation. To date, nsP3 has been demonstrated to mediate many virus–host protein–protein interactions in several fundamental alphavirus mechanisms, particularly during the early stages of replication. However, the molecular pathways and proteins networks underlying these mechanisms remain poorly described. This is due to the low genetic sequence homology of the nsP3 protein among the alphavirus species, especially at its 3′ C-terminal domain, the hypervariable domain (HVD). Moreover, the nsP3 HVD is almost or completely intrinsically disordered and has a poor ability to form secondary structures. Evolution in the nsP3 HVD region allows the alphavirus to adapt to vertebrate and insect hosts. This review focuses on the putative roles and functions of indel, repetition, and duplication events that have occurred in the alphavirus nsP3 HVD, including characterization of the differences and their implications for specificity in the context of virus–host interactions in fundamental alphavirus mechanisms, which have thus directly facilitated the evolution, adaptation, viability, and re-emergence of these viruses.
