Abstract
Pneumoviruses include pathogenic human and animal viruses, the most known and studied being the human respiratory syncytial virus (hRSV) and the metapneumovirus (hMPV), which are the major cause of severe acute respiratory tract illness in young children worldwide, and main pathogens infecting elderly and immune-compromised people. The transcription and replication of these viruses take place in specific cytoplasmic inclusions called inclusion bodies (IBs). These activities depend on viral polymerase L, associated with its cofactor phosphoprotein P, for the recognition of the viral RNA genome encapsidated by the nucleoprotein N, forming the nucleocapsid (NC). The polymerase activities rely on diverse transient protein-protein interactions orchestrated by P playing the hub role. Among these interactions, P interacts with the NC to recruit L to the genome. The P protein also plays the role of chaperone to maintain the neosynthesized N monomeric and RNA-free (called N0) before specific encapsidation of the viral genome and antigenome. This review aims at giving an overview of recent structural information obtained for hRSV and hMPV P, N, and more specifically for P-NC and N0-P complexes that pave the way for the rational design of new antivirals against those viruses.
Highlights
Institut de Chimie des Substances Naturelles, CNRS, Université Paris-Saclay, 91190 Gif-sur-Yvette, France; These authors contributed to this work
A major advance was made with the purification of a recombinant chimeric protein corresponding to full-length N fused with the N-terminal domain of P, which allowed the resolution of the X-ray crystal structure of the human metapneumovirus (hMPV) N0 -P complex (Figure 7) [87]
The recent advances in the structure of the viral proteins associated with the L polymerase of pneumoviruses pave the way for the development of new antiviral strategies
Summary
Publisher’s Note: MDPI stays neutral with regard to jurisdictional claims in published maps and institutional affiliations. Mononegavirales have a non-segmented negative-sense RNA genome ranging from 13.2 to 15.3 kb They form a large group exhibiting common genome organization and sharing similar replication mechanisms. The former paramyxoviral subfamily Pneumovirinae was elevated to family status Pneumoviridae [2]. The Orthopneumovirus genus groups human respiratory syncytial virus (hRSV), bovine respiratory syncytial virus (bRSV), and pneumonia virus of mice (PVM). Sequencing of pooled nasal swabs in feral swine in the USA [4]. For hMPV, and 43.3% for aMPV, respectively, indicating that the PVM/SOV group is distinct from Meta- and Ortho-pneumoviruses and could constitute a third genus
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