Animal epidemic diseases are the primary threat to the livestock industry. Of the veterinary pathogens that cause these diseases, viruses are responsible for approximately half of the most important animal diseases, according to the OIE's (Office of International Epizootic) classification of terrestrial and aquatic notifiable animal diseases (1). Animal viruses are divided into DNA and RNA viruses on the basis of the genetic materials, both the viruses are the dominate pathogens that affecting animal production in livestock industry (1, 2). The differences between DNA and RNA viruses include their lifetimes in target cells, how they attach to and enter host cells, and their biosynthesis, maturation, and release from cells (2, 3).

Compared with DNA viruses, RNA viruses have a higher mutation rate and cause more serious economic damage in the livestock industry (4). Lower mutation rates of DNA viruses were usually influence by the viral genome and DNA repairing protein that benefit for proofread and correct replication errors (5). Oppositely, offspring of RNA viruses are usually produced 1 ± 2 mutations compared with their parent. RNA virus usually producing a mutant cloud of descendants in extremely environment (5). RNA viruses are also divided into avian, mammalian, and zoonotic viruses in domestic animal industries. For example, the avian leukosis retrovirus causes great losses in the avian industry and many subgroups have been isolated in recent years (6–12). In mammals, more RNA viruses are also being reported, of which the classical swine fever virus and porcine reproductive and respiratory syndrome virus (PRRSV) are the main RNA viruses that cause great losses in porcine industries. Because of their high mutation rates and the additional subgroups identified in recent years (13–17), both viruses are difficult to eliminate. Some RNA viruses not only infect animals but also humans, with the influenza virus the most typical RNA zoonotic virus. For example, H5N1 and H9N2 subgroups of the influenza virus are the main infectious pathogens affecting both humans and animals (18–23). To reduce economic losses in animal industries, the main approaches are to reduce the virus titer in animals and to improve their immunity. Thus, an understanding of the mechanism that clears RNA viruses from target cells is the most important step in controlling virus infection.

RNA interference (RNAi) is an important mechanism in mediating the clearance of RNA viruses (24). Viral RNA can be degraded through the inhibition of viral replication by the binding effects between small interfering RNAs and viral nucleic acids (24, 25). Generally, the antiviral effects due to RNAi are typically found in invertebrates, and RNAi functioning as an antiviral effector has only been detected in undifferentiated stem cells (26, 27). RNAi also plays important roles in the activation of IFN-I (Type I interferon) and its antiviral effectors (IFN-stimulated genes), with those genes producing the main antiviral effects in differentiated vertebrate somatic cells (Figure 1) (28).

RNA virus replication and clearance are typically influenced by several factors, of which miRNAs produced in cells may play important roles in a regulated network. miRNAs usually bind to the miRNA binding sites within mRNAs and viral genomes to exert their regulatory function (29, 30). The number of miRNA binding sites within a viral genome affects the viral replication (Figure 1). Most miRNA binding sites are in the 5' and 3' non-translation regions (NTRs) of a viral genome (31), but the sites were also recently found in the translated regions (32, 33). An increase in the number of perfect complementary miRNA binding sites in the NTRs of RNA viruses causes strong translational repression in vitro and a decrease in virulence in mice (34). miRNA gene translation is also influenced by epigenetic and environmental conditions (34, 35). For example, compared with primary tissues, low levels of miRNAs are detected in cultural cells, especially in a high confluency (36). Furthermore, non-canonical miRNA target sites in specific cells are also potential factors that affect miRNA production and therefore RNA virus replication (25).

Direct inhibition effects of miRNAs on viruses were previous recognized as an effective way in invertebrates rather than in vertebrates, subsequent studies confirmed the anti-viral function of miRNAs in undifferential vertebrates' stem cells. But the direct viral inhibition effect of miRNAs was controversial in somatic Cells (37). Cullen's studies evaluated the directly viral genome targeting effects of miRNAs and his research revealed viruses induced miRNAs are hardly causing reduction of virus copy number (38–40). Recently study summarized the potential directly viral genome targeting effects of miRNAs. Trobaugh's review analyzed the direct inhibitory effects of miRNAs. And the review point out that direct inhibitory effects of miRNAs on viruses are primarily concentrated in the viral genome and in viral genome translation (Figure 1) (31, 41). There are so many reasons causing direct targeting reduction of miRNAs, of which viruses escaping mechanism, incomplete pairing of miRNA and viruses mutation are the important reasons. But the artificial application of miRNAs on viruses genome were reported as an important method to reduce viral replication copies recently.

Direct inhibitory effects of miRNAs on viruses mainly play its roles in viral genome and in viral genome translation. Positive-strand RNA viruses release their genomes into the cytoplasm after entering cells following recognition by receptors within the membrane surface (41). Similar to mRNA produced in a cell, the released viral RNA is either decayed or replicated when combined with miRNAs in the cytoplasm. For example, the expression of miR-181, miR-206, miR-23, and miR-378 in specific cells can inhibit the replication of PRRSV by binding to the viral genome (42, 43). By contrast, miR-17 and let-7c bind to the 3' NTR of the bovine viral diarrhea virus genome and cause virus genome translation and an increase in RNA stability rather than translational repression (41). Similar effects are also found in negative-strand viruses. The negative-stand RNA released in the cytoplasm is first translated into positive-stand RNA for protein synthesis and virus assembly. The translated positive RNA can recruit miRNA binding to the miRNA-recognized sites and ultimately influence virus replication and assembly (25). For example, the influenza PB1 gene recruits miR-323, miR-491, miR-485, miR-654, and miR-3145, which leads to RNA degradation in infected human and canine epithelial cell lines in vitro (33, 44, 45).

To determine the indirect effects of miRNAs on virus infection, the primary focus is on the level of miRNAs and the changes in host immunity response in target cells (Figure 1) (46). Specifically, an immune response initiated by a virus mediates viral-recognition receptors that lead to activation of translation factors and ultimately changes in the expression profiles of miRNAs (47, 48). For example, changes in the expression of specific miRNAs (miR-151-5p and miR-223-3p) determine whether the H5N2 influenza virus is pathogenic or is attenuated (49). Changes in specific miRNAs also affect miRNA-mediated protein expression (50). The IFN systems are a crucial mechanism in the removal of viral infection (25). Virus-mediated regulation of the IFN signaling cascade is controlled by miRNA levels in target cells (25). For example, miR-23 and miR-505 can increase IFN-α/β expression, which is useful in clearing PRRSV (42, 43). By contrast, with the expression of miR-23b, avian leukosis viral infection in chicken spleen downregulates IFN regulatory factor 1 levels and innate immune induction (51). Thus, the miRNAs that are involved in downregulating the innate immune response during RNA virus infections need to be identified in the future.

Though the indirect effects of miRNAs on RNA viral infection were widely confirmed and recognized, the direct effects of miRNAs were still controversial. This controversy was mainly concentrated on several factors. Firstly, miRNAs were reducible generated from the cells after the viruses infection, but these miRNAs were hardly presented its' directly target effects on viral genome because of the low level of miRNAs produced by the target cells. The other factor is the potential escaping mechanism of viral and the cells complex immune system. The mismatch of miRNAs and viral genome mutation also reduced its inhibition effects.

MOV10 is an important SF-1, ATP-dependent RNA helicase in the UPF1p family (52–55), originally identified as a protein that prevents Moloney murine leukemia virus infection in mice. Two potential mechanisms can explain the antiviral bioactivity of MOV10: (1) regulating antiviral gene expression so as to achieve antiviral capacity (56) and (2) changing miRNA expression directly or indirectly so as to mediate viral clearance effects (46). The two mechanisms are discussed below in detail.

The antiviral activity of MOV10 during RNA virus infection is discussed in this review. Overall, the antiviral capacity of MOV10 is primarily reflected in two important mechanisms. First, MOV10 weakens viral virulence by binding the related protein, thereby activating IFN signal and cell autophagy pathways. Second, MOV10 functions as an RNA helicase during RNA virus infection. MOV10 regulates miRNA and mRNA generation, maturation, and degradation by miRNA pathways, which influence virus replication and packaging. The two mechanisms are typically coordinated in different virus infection stages. In addition, the number of studies is increasing that confirm MOV10 not only has important roles in infection by human viruses, such as HIV and human hepatitis delta virus, but also shows antiviral activity against animal RNA viruses. The antiviral ability of MOV10 and the related pathways during animal RNA virus infection are worthy of future attention. It is also can be used as an important tools for reduction of animal RNA viruses infection in future.

FS, XL, and YJ conceived the study and wrote the manuscript. All authors contributed to the article and approved the submitted version.

The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.