Tohoku J. Exp. Med., 2019 August, 248(4)

Review

Rotavirus Replication: Gaps of Knowledge on Virus Entry and Morphogenesis

HIROSHI SUZUKI1

1Niigata Seiryo University, Niigata, Niigata, Japan

In 1973, rotaviruses A (RVAs) were discovered as major causative agents of acute gastroenteritis in infants and young children worldwide. The infectious RV virion is an icosahedral particle composed of three concentric protein layers surrounding the 11 double-stranded (dsRNA) segments. An in vitro replication system for RVs in permanent cell lines was developed in 1982 and expanded to replication in intestinal organoids in 2015. However, the details of rotavirus (RV) entry into cells and particle maturation mechanisms at the molecular level remain incompletely understood. Slowing down human RVA replication in cell culture on ice allowed morphological visualization of virus particle entry and the assembly of triple-layered particles (virion). Although RVAs are non-enveloped viruses, after virus attachment to the cell membrane, the virus enters the cell by perforating the plasma membrane by a fusion mechanism involving VP5* of the cleaved VP4 protein, as the alternative virus entry route besides the receptor-mediated endocytosis which is generally accepted. After assembling double-layered particles (DLPs) in viroplasm or cytoplasm, they appear to be connected with the endoplasmic reticulum (ER) membrane and become coated with outer capsid proteins (VP4 and VP7) in a coating process. The perforation of the ER membrane is caused by an unknown mechanism following interaction between non-structural protein 4 (NSP4) and the inner capsid protein VP6 of the DLPs. The coating process is closely related to the formation of a hetero-oligomeric complex (NSP4, VP4 and VP7). These lines of evidence suggest the existence of novel mechanisms of RV morphogenesis.

Key words —— membrane penetration; morphogenesis; recoating; rotavirus; virus cell entry

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Tohoku J. Exp. Med., 2019, 248, 285-296

Correspondence: Hiroshi Suzuki, Niigata Seiryo University, 1-5939 Suido-Cho, Chuo-Ku, Niigata, Niigata 951-8121, Japan.

e-mail:hsuzuki@n-seiryo.ac.jp