The name porcine reproductive and respiratory syndrome virus (PRRSV) NADC30-like was first coined in 2015. It originated from the NADC30 strain that was introduced into China by importing breeding pigs and has since undergone mutations or recombination, resulting in variant viruses. Following widespread outbreaks in China in recent years, these NADC30-like strains have presented major health challenges in swine production systems. Outcomes induced by PRRSV NADC30-like infection are highly variable, ranging from inapparent to severe, depending on the recombination between NADC30 and field PRRSV strains prevalent in swine farms. Vaccines and strict biosecurity measures have been explored to fight this disease; however, current PRRSV commercially modified-live virus vaccines (MLVs) have the potential to revert to virulence and only provide limited or no cross-protection efficacy against NADC30-like strains. PRRSVs will remain an ongoing challenge to the swine industry until safe and effective vaccines or antiviral reagents are developed.

Background: Our previous studies have demonstrated that piglets infected with highly pathogenic porcine reproductive and respiratory syndrome virus (HP-PRRSV) may develop significant thymus atrophy, which related to thymocytes apoptosis. However, apart from that detected in the thymus, there are no reports describing cell apoptosis induced by HP-PRRSV infection. In this study, we analyzed comparatively the pathological changes, cell apoptosis and viral load in peripheral immune organs including tonsil, inguinal lymph nodes (ILNs) and spleen and lungs following experimental infection of piglets with HP-PRRSV HuN4 and classical PRRSV CH-1a. Findings: HP-PRRSV HuN4 exhibited much stronger cell tropism than CH-1a in immune organs and lungs of piglets. HuN4 infection led to the serious injuries in tonsils, ILNs, spleens and lungs, especially apoptosis in these organs was significant. Conclusions: HuN4 infection induced severe lesions (gross pathology, histopathology and cell apoptosis) in the peripheral immune organs and lungs of infected piglets. Large numbers of apoptotic cells in immune organs and lung induced by HuN4 may play a role in the pathogenesis of the HP-PRRS and the distinct injuries caused by HuN4 infection may be associated with the high mortality rate of HP-PRRS in pigs.

Porcine reproductive and respiratory syndrome virus (PRRVS) is a major swine viral pathogen that affects the pig industry worldwide. Control of early PRRSV infection is essential, and different types of PRRSV-positive samples can reflect the time point of PRRSV infection. This study aims to investigate the epidemiological characteristics of PRRSV in China from Q4 2021 to Q4 2022, which will be beneficial for porcine reproductive and respiratory syndrome virus (PRRSV)control in the swine production industry in the future. A total of 7518 samples (of processing fluid, weaning serum, and oral fluid) were collected from 100 intensive pig farms in 21 provinces, which covered all five pig production regions in China, on a quarterly basis starting from the fourth quarter of 2021 and ending on the fourth quarter of 2022. Independent of sample type, 32.1% (2416/7518) of the total samples were PCR-positive for PRRSV, including 73.6% (1780/2416) samples that were positive for wild PRRSV, and the remaining were positive for PRRSV vaccine strains. On the basis of the time of infection, 58.9% suckling piglets (processing fluid) and 30.8% weaning piglets (weaning serum) showed PRRSV infection at an early stage (approximately 90% of the farms). The sequencing analysis results indicate a wide range of diverse PRRSV wild strains in China, with lineage 1 as the dominant strain. Our study clearly demonstrates the prevalence, infection stage, and diversity of PRRSV in China. This study provides useful data for the epidemiological understanding of PRRSV, which can contribute to the strategic and systematic prevention and control of PRRSV in China.

The current vaccines for porcine reproductive and respiratory syndrome virus (PRRSV) have failed to provide broad protection against infection by various strains of PRRSV. Porcine Interleukin-4 (pIL-4) plays an important role in the regulation of the immune response and has been used previously as an immunological adjuvant. The objective of this study was to construct a recombinant PRRSV expressing pIL-4 and to evaluate the immune response of the recombinant virus in piglets. The pIL-4 gene was inserted in the PRRSV (CH-1R strain) infectious clone by overlap PCR. Indirect immunofluorescence assay (IFA) and Western blotting were used to confirm the recombinant virus. The stability of the recombinant virus was assessed by DNA sequencing and IFA after 15 passages in vitro. Recombinant virus was injected into pigs and efficacy of immune protection was evaluated in comparison with the parental virus. The recombinant virus (CH-1R/pIL-4) was successfully rescued and shown to have similar growth kinetics as the parental virus. The recombinant virus was stable for 15 passages in cell culture. Pigs vaccinated with CH-1R/pIL-4 produced a similar humoral response to the response elicited by parental virus, but IL-4 level in the supernatant of PBMCs from pigs vaccinated with CH-1R/pIL-4 was significantly higher than the parent virus at 28 days post-immunization (DPI). Flow cytometric (FCM) analysis showed that the percentage of CD4+CD8+ double positive T (DPT) cells in the CH-1R/pIL-4 vaccinated group was significantly higher than the parental virus at 3 and 7 Days Post-Challenge (DPC), and the IL-4 level in the blood significantly increased at 7 DPC. However, the viral load and histopathology did not show significant difference between the two groups. A recombinant PRRSV expressing porcine IL-4 was rescued and it remained genetically stable in vitro. The recombinant virus induced higher DPT ratios and IL-4 levels in the blood after HP-PRRSV challenge compared to the parental virus in piglets. However, it did not significantly improve protection efficacy of PRRSV vaccine.

The inability of current vaccines to provide effective protection against porcine reproductive and respiratory syndrome virus (PRRSV) infection is not fully understood. One of the reasons might be the presence of anti-idiotypic antibodies (Ab2s) to the envelope glycoprotein GP5 induced by PRRSV infection since our previous studies demonstrated the presence of auto-Ab2s (aAb2s) in pigs infected with PRRSV. To test this hypothesis, PRRSV negative piglets were injected with a monoclonal Ab2 (Mab2-5G2) and aAb2s that are specific for anti-GP5 antibody, vaccinated with the attenuated PRRSV vaccine CH-1R and then challenged with the highly pathogenic PRRSV HuN4 strain. The animals were evaluated for clinical signs, pathological changes of the thymus and lungs, viremia, levels of serum antibodies and cytokines. The piglets injected with Mab2-5G2 or aAb2, and who received the attenuated PRRSV vaccine CH-1R before challenge, produced high levels of anti-N antibodies, IL-2 and IL-4, but low levels of neutralizing antibodies. After PRRSV HuN4 challenge, the animals showed obvious clinical signs, including lung lesions, severe thymus atrophy and decreased production of IL-4 and higher level of viremia. When anti-GP5 Ab2s are present, the use of attenuated PRRSV vaccine CH-1R against HP-PRRSV infection is not recommended. It can result in poor health status with pneumonia and thymus atrophy.