During the co-evolution of viruses and their hosts, viruses have developed various strategies for overcoming host immunological defenses so that they can proliferate efficiently. Porcine reproductive and respiratory syndrome virus (PRRSV), a significant virus to the swine industry across the world, typically establishes prolonged infection via diverse and complicated mechanisms, which is one of the biggest obstacles for controlling the associated disease, porcine reproductive and respiratory syndrome (PRRS). In this review, we summarize the latest research on how PRRSV circumvents host antiviral responses from both the innate and adaptive immune systems and how this virus utilizes other evasion mechanisms, such as the manipulation of host apoptosis and microRNA. A thorough understanding of the exact mechanisms of PRRSV immune evasion will help with the development of novel antiviral strategies against PRRSV.

NADC30-like strains of porcine reproductive and respiratory syndrome virus (PRRSV) were firstly reported in China in 2013. Since then, these strains have been epidemic in more than 13 provinces/regions. During 2016-2017, a total of 18 PRRSV isolates were obtained from 52 clinical samples in Henan province. Based on comparative and phylogenetic analyses of ORF5 and partial Nsp2 genes, 83.3% (15/18) isolates belonged to NADC30-like strains, and the ORF5 shared 87.4%-95.5% nucleotide identity with NADC30/JL580 and 84.2%-89.9% with JXA1/CH-1a, respectively. The genetic variation analysis showed that extensive amino acid substitutions happened in the significant regions of ORF5 including major linear antigenic epitopes (27-30aa, 37-45aa, 52-61aa) and the potential N-glycosylation sites (32-35aa). 16.7% (3/18) isolates were very close to HP-PRRSV derived attenuated strains. Moreover, these three isolates shared common residues at the positions 33D, 59 N, 164R, 196R in ORF5 and 303D, 399T, 575V, 598R, 604G in Nsp2, which were thought to be unique to modified live vaccines (MLVs) or their derivatives. Therefore, they were probably the revertants from MLVs. Our studies showed that the HP-PRRSV strains seemed to be gradually disappearing and NADC30-like strains had become the main causative agents of PRRS in central China. Comparing with HP-PRRSVs, the ORF5 of NADC30-like PRRSV strains displayed extensive amino acid mutations which may be related with immune evasion. Furthermore, the circulation of MLV derivatives in the fields made the diagnosis and control of PRRSV more complicated.

Once infected by viruses, cells can detect pathogen-associated molecular patterns (PAMPs) on viral nucleic acid by host pattern recognition receptors (PRRs) to initiate the antiviral response. Porcine reproductive and respiratory syndrome virus (PRRSV) is the causative agent of porcine reproductive and respiratory syndrome (PRRS), characterized by reproductive failure in sows and respiratory diseases in pigs of different ages. To date, the sensing mechanism of PRRSV has not been elucidated. Here, we reported that the pseudoknot region residing in the 3′ untranslated regions (UTR) of the PRRSV genome, which has been proposed to regulate RNA synthesis and virus replication, was sensed as nonself by retinoic acid-inducible gene I (RIG-I) and Toll-like receptor 3 (TLR3) and strongly induced type I interferons (IFNs) and interferon-stimulated genes (ISGs) in porcine alveolar macrophages (PAMs). The interaction between the two stem-loops inside the pseudoknot structure was sufficient for IFN induction, since disruption of the pseudoknot interaction powerfully dampened the IFN induction. Furthermore, transfection of the 3′ UTR pseudoknot transcripts in PAMs inhibited PRRSV replication in vitro . Importantly, the predicted similar structures of other arterivirus members, including equine arteritis virus (EAV), lactate dehydrogenase-elevating virus (LDV), and simian hemorrhagic fever virus (SHFV), also displayed strong IFN induction activities. Together, in this work we identified an innate recognition mechanism by which the PRRSV 3′ UTR pseudoknot region served as PAMPs of arteriviruses and activated innate immune signaling to produce IFNs that inhibit virus replication. All of these results provide novel insights into innate immune recognition during virus infection. IMPORTANCE PRRS is the most common viral disease in the pork industry. It is caused by PRRSV, a positive single-stranded RNA virus, whose infection often leads to persistent infection. To date, it is not yet clear how PRRSV is recognized by the host and what is the exact mechanism of IFN induction. Here, we investigated the nature of PAMPs on PRRSV and the associated PRRs. We found that the 3′ UTR pseudoknot region of PRRSV, which has been proposed to regulate viral RNA synthesis, could act as PAMPs recognized by RIG-I and TLR3 to induce type I IFN production to suppress PRRSV infection. This report is the first detailed description of pattern recognition for PRRSV, which is important in understanding the antiviral response of arteriviruses, especially PRRSV, and extends our knowledge on virus recognition.