Rotavirus (RV) is the major causes of severe diarrhea in infants and young children under five years of age. There are no effective drugs for the treatment of rotavirus in addition to preventive live attenuated vaccine. Recent evidence demonstrates that microRNAs (miRNAs) can affect RNA virus replication. However, the antiviral effect of miRNAs during rotavirus replication are largely unknown. Here, we determined that miR-7 is upregulated during RV replication and that it targets the RV NSP5 (Nonstructural protein 5). Results suggested that miR-7 affected viroplasm formation and inhibited RV replication by down-regulating RV NSP5 expression. Up-regulation of miR-7 expression is a common regulation method of different G-type RV-infected host cells. Then, we further revealed the antiviral effect of miR-7 in diarrhea suckling mice model. MiR-7 is able to inhibit rotavirus replication in vitro and in vivo. These data provide that understanding the role of cellular miR-7 during rotaviral replication may help in the identification of novel therapeutic small RNA molecule drug for anti-rotavirus.

Neonatal rhesus monkeys as an animal model for rotavirus infection

The strategies for developing rotavirus (RV) vaccines have always been controversial. At present, both the monovalent RV vaccine and the multivalent RV vaccine have displayed excellent safety and efficacy against RV infection and shown cross-reactive immunity, which laid the question whether the multivalent RV vaccine could be replaced by the monovalent RV vaccine. In this study, we focused on comparing the immunogenicity (serum neutralization activity and protection against homotypic and heterotypic RVs’ challenge) of individual standard RV strains (monovalent RV immunogens) and different combinations of them (multivalent RV immunogens). In result, RV immunogens showed general immunogenicity and heterotypic reaction but the multivalent RV immunogens exhibited greater serum neutralization activity and stronger heterotypic reaction than the monovalent RV immunogens (P<0.05). As to the protection, the multivalent RV immunogens also revealed more rapid and stronger protection against homotypic and heterotypic RVs’ challenge than the monovalent RV immunogens. The results demonstrated that both the monovalent and multivalent RV immunogens exhibited high immunogenicity, but the monovalent RV immunogens could not provide enough neutralization antibodies to protect MA104 cells against the infection with heterotypic RV strains and timely protection against homotypic and heterotypic RVs, so the multivalent RV vaccine could not be replaced by the monovalent RV vaccine.

Live-attenuated rotavirus vaccine has shown low protection in underdeveloped or developing countries. However, the inactivated rotavirus vaccine may have the potential to overcome some of these challenges. In the present study, the immunogenicity and protective efficacy of a bivalent inactivated rotavirus vaccine by parenteral administration were elevated in a neonatal rhesus monkey model. A bivalent inactivated rotavirus vaccine containing G1P[8] (ZTR-68 strain) and G9P[8] (ZTR-18 strain) was administered to pregnant rhesus monkeys twice at an interval of 14 days. Neutralizing antibodies against RV strains ZTR-68, ZTR-18, SA11, WA, UK, and Gottfried emerged in pregnant rhesus monkeys and were transplacentally transmitted to the offspring. In the vaccine group, clinical symptoms of diarrhea, viral load in the gut tissue and histopathological changes were significantly reduced in the neonatal rhesus monkeys following oral challenge with the SA11 strain.