Efficacy of Type 2 porcine reproductive and respiratory syndrome virus (PRRSV) vaccine against the 2010 isolate of Vietnamese highly pathogenic PRRSV challenge in pigs

ABSTRACT During the past 2 years, an atypical clinical outbreak, caused by a highly pathogenic porcine reproductive and respiratory syndrome virus (PRRSV) with a unique 30-amino-acid deletion in its Nsp2-coding region, was pandemic in China. In this study, we generated four full-length infectious cDNA clones: a clone of the highly virulent PRRSV strain JXwn06 (pWSK-JXwn), a clone of the low-virulence PRRSV strain HB-1/3.9 (pWSK-HB-1/3.9), a chimeric clone in which the Nsp2 region containing the 30-amino-acid deletion was replaced by the corresponding region of the low-virulence PRRSV strain HB-1/3.9 (pWSK-JXwn-HB1nsp2), and a mutated HB-1/3.9 clone with the same deletion in Nsp2 as JXwn06 (pWSK-HB1-ND30). We also investigated the pathogenicities of the rescued viruses (designated RvJXwn, RvJXwn-HB1nsp2, RvHB-1/3.9, and RvHB1-ND30, respectively) in specific-pathogen-free piglets in order to determine the role of the 30-amino-acid deletion in the virulence of the highly pathogenic PRRSV. All the rescued viruses could replicate stably in MARC-145 cells. Our findings indicated that RvJXwn-HB1nsp2 retained high virulence for piglets, like RvJXwn and the parental virus JXwn06, although the survival time of piglets infected with RvJXwn-HB1nsp2 was obviously prolonged. RvHB1-ND30 exhibited low virulence for piglets, like RvHB-1/3.9 and the parental virus HB-1/3.9. Therefore, we conclude that the 30-amino-acid deletion is not related to the virulence of the highly pathogenic PRRSV emerging in China.

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Immunity against a Japanese local strain of porcine reproductive and respiratory syndrome virus decreases viremia and symptoms of a highly pathogenic strain

BMC Veterinary Research ◽

10.1186/s12917-021-02863-4 ◽

2021 ◽

Vol 17 (1) ◽

Author(s):

Hiroshi Iseki ◽

Kenji Kawashima ◽

Tomoyuki Shibahara ◽

Masaji Mase

Keyword(s):

Amino Acid ◽

Local Strain ◽

Daily Weight Gain ◽

Respiratory Syndrome Virus ◽

Nucleotide Sequence Analysis ◽

Amino Acid Deletion ◽

Highly Pathogenic ◽

Group 3 ◽

Group 2

Abstract Background The type 2 highly pathogenic porcine reproductive and respiratory syndrome virus (HP-PRRSV) has spread throughout countries of southeast Asia, where it has caused severe economic losses. Even countries presently free of PRRSV are at high risk for infection and spread of this virus. Some of these countries, including Japan, have broad epidemics of the local type 2 PRRSV, creating chronic pathogenicity in the domestic pig population. The present study aimed to evaluate the protective efficacy of immunity by infection with a Japanese field isolate, EDRD1, against heterologous challenge with a Vietnamese HP-PRRSV field strain. To this end, four groups of PRRSV-negative crossbreed piglets were used for a challenge study. Groups 1 and 2 were inoculated with EDRD1 via the intranasal route. After 26 days, Groups 2 and 3 were inoculated with HP-PRRSV via the same route. Group 4 served as an uninfected control. Blood and oral fluid samples were taken every 3–4 days after HP-PRRSV challenge; on day 16 post-challenge, all pigs were euthanized, and examined pathologically. Results The nucleotide sequence analysis of nonstructural protein 2 gene of EDRD1 and comparison with Vietnamese HP-PRRSV showed that the 39 amino acid deletion sites of EDRD1 was nearly in the same region as the 29 amino acid deletion sites of HP-PRRSV. Immunity conferred by inoculation with EDRD1 dramatically reduced viral load in the sera and tissues besides viral shedding (Group 2) compared with those in pigs infected only with HP-PRRSV (Group 3). The clinical signs and rectal temperature were significantly reduced, and the average daily weight gain was significantly improved in the EDRD1-inoculated pigs (Group 2) compared with the Group 3 pigs. Notably, no viral RNA was detected in various organs of the Group 2 pigs 16 days post-infection with HP-PRRSV, except in one pig. Therefore, the immunity induced by EDRD1 and its genetically close field isolates may play a role in reducing viremia caused by HP-PRRSV. Conclusions The results of the present study demonstrate that pigs are highly protected against heterologous Vietnamese HP-PRRSV challenge by immunity against a Japanese local strain, EDRD1.

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An infectious cDNA clone of a highly pathogenic porcine reproductive and respiratory syndrome virus variant associated with porcine high fever syndrome

Journal of General Virology ◽

10.1099/vir.0.2008/001529-0 ◽

2008 ◽

Vol 89 (9) ◽

pp. 2075-2079 ◽

Cited By ~ 52

Author(s):

Jian Lv ◽

Jianwu Zhang ◽

Zhi Sun ◽

Weiquan Liu ◽

Shishan Yuan

Keyword(s):

Clinical Symptoms ◽

Animal Experiments ◽

High Fever ◽

Respiratory Syndrome Virus ◽

Cdna Clones ◽

Highly Pathogenic ◽

Virus Variant ◽

Recombinant Viruses ◽

Prrsv Strain ◽

Highly Pathogenic Prrsv

Since May 2006, a so-called ‘porcine high fever syndrome’ (PHFS) has spread all over China. The arterivirus porcine reproductive and respiratory syndrome virus (PRRSV) was believed to be the main causative agent, although the involvement of other pathogens was not formally excluded. The genome of a representative Chinese PRRSV strain, named JX143, was sequenced and used to develop infectious cDNA clones, pJX143 and pJX143M, with the latter containing an engineered MluI site that served as a genetic marker. In various virological assays, the rescued viruses, vJX143 and vJX143M, were indistinguishable from their parental virus. Animal experiments showed that these recombinant viruses retained the high pathogenicity and induced the typical clinical symptoms observed during PHFS outbreaks. This is the first report describing infectious cDNA clones of this highly pathogenic PRRSV. Our results unambiguously fulfil Koch's postulates and define highly pathogenic PRRSV as the aetiological agent of PHFS in China.

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Porcine Reproductive and Respiratory Syndrome Virus Structural Protein GP3 Regulates Claudin 4 To Facilitate the Early Stages of Infection

Journal of Virology ◽

10.1128/jvi.00124-20 ◽

2020 ◽

Vol 94 (20) ◽

Author(s):

Guofei Ding ◽

Jiaqi Liu ◽

Qingyuan Shao ◽

Bin Wang ◽

Jian Feng ◽

...

Keyword(s):

Transcription Factor ◽

Respiratory Syndrome Virus ◽

Structural Protein ◽

Extracellular Loop ◽

Highly Pathogenic ◽

Early Stages ◽

Transcription Factor Sp1 ◽

Viral Particles ◽

Highly Pathogenic Prrsv ◽

Novel Therapeutic

ABSTRACT Claudins (CLDN) are a family of proteins that represent the most important components of tight junctions, where they establish the paracellular barrier that controls the flow of molecules in the intercellular space between epithelial cells. Several types of viruses make full use of CLDN to facilitate entry into cells. Porcine reproductive and respiratory syndrome virus (PRRSV) is one of the most important pathogens in the swine industry. In this study, we found that CLDN4 functions as an anti-PRRSV factor by blocking its absorption during the early stages of infection. The small extracellular loop (ECL2) of CLDN4 restricted the viral particles outside cells by binding to GP3. A novel function of GP3-mediated regulation of CLDN4 transcription was suggested. CLDN4 can be decreased through downregulating the level of CLDN4 transcription by ubiquitinating the transcription factor, SP1. The mechanism by which highly pathogenic PRRSV infects the epithelium was proposed. Importantly, ECL2 was found to block PRRSV absorption and infection and neutralize the virus. A more in-depth understanding of PRRSV infection is described, and novel therapeutic antiviral strategies are discussed. IMPORTANCE In the present study, the role of CLDN4 in PRRSV infection was studied. The results showed that CLDN4 blocked absorption into cells and restricted extracellular viral particles via the interaction between the CLDN4 small extracellular loop, ECL2, and the viral surface protein GP3. GP3 was found to downregulate CLDN4 through ubiquitination of the transcription factor SP1 to facilitate viral entry. The mechanism by which highly pathogenic PRRSV infects the epithelium is suggested. A novel function of GP3 in regulating gene transcription was discovered. Moreover, ECL2 could block PRRSV absorption and infection, as well as neutralizing the virus in the supernatant, which may lead to the development of novel therapeutic antiviral strategies.

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Dynamic Changes in Inflammatory Cytokines in Pigs Infected with Highly Pathogenic Porcine Reproductive and Respiratory Syndrome Virus

Clinical and Vaccine Immunology ◽

10.1128/cvi.00517-09 ◽

2010 ◽

Vol 17 (9) ◽

pp. 1439-1445 ◽

Cited By ~ 63

Author(s):

Yonggang Liu ◽

Wenda Shi ◽

Enmin Zhou ◽

Shujie Wang ◽

Shouping Hu ◽

...

Keyword(s):

Immune Responses ◽

Inflammatory Cytokines ◽

Peripheral Blood ◽

Interleukin 1 ◽

Respiratory Syndrome Virus ◽

Necrosis Factor Alpha ◽

Highly Pathogenic ◽

Cytokine Levels ◽

Loss Of Appetite ◽

Highly Pathogenic Prrsv

ABSTRACT Porcine reproductive and respiratory syndrome virus (PRRSV) infection induces both humoral and cellular immune responses. In this study, we investigated the changes in cytokine levels in peripheral blood between the highly pathogenic PRRSV HuN4 strain and its derivative strain HuN4-F112 obtained by serial propagation in MARC145 cells to 112 passages. The results demonstrated that pigs infected with HuN4 showed a loss of appetite, decrease in body weight, raised body temperature, and respiratory symptoms, along with interstitial pneumonia lesions. The PRRSV amounts in the pigs infected with HuN4 were 105 to 109 copies/ml in the blood and 1010 to 1011 copies/g in the lung tissues, whereas the virus amounts with HuN4-F112 were 102.15 to 103.13 copies/ml in the blood and 103.0 to 103.6 copies/g in the lungs. Moreover, the levels of interleukin 1 (IL-1), IL-6, tumor necrosis factor alpha (TNF-α), and alpha interferon (IFN-α) in peripheral blood were upregulated 7 days postinoculation with HuN4, which was earlier than in the HuN4-F112 group. Furthermore, cytokine levels in the pigs infected with HuN4 returned to normal on the 21st day postinoculation, while the levels in those infected with HuN4-F112 continued to increase. These results demonstrated that the pigs infected with the highly pathogenic PRRSV HuN4 strain generated earlier and higher levels of inflammatory cytokines, and the results also indicated that HuN4 may aggravate inflammation and damage tissues and organs. The low-pathogenic PRRSV HuN4-F112 strain induced lower levels of inflammatory cytokines, which may enhance the immune responses against the infection.

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Efficacy of a live attenuated highly pathogenic PRRSV vaccine against a NADC30-like strain challenge: implications for ADE of PRRSV

BMC Veterinary Research ◽

10.1186/s12917-021-02957-z ◽

2021 ◽

Vol 17 (1) ◽

Author(s):

Xin-xin Chen ◽

Xinyu Zhou ◽

Tengda Guo ◽

Songlin Qiao ◽

Zhenhua Guo ◽

...

Keyword(s):

Neutralizing Antibodies ◽

Molecular Mechanisms ◽

Clinical Signs ◽

Bodyweight Gain ◽

Economic Losses ◽

Respiratory Syndrome Virus ◽

Experimental Conditions ◽

Highly Pathogenic ◽

Highly Pathogenic Prrsv

Abstract Background Porcine reproductive and respiratory syndrome virus (PRRSV) infection can cause severe reproductive failure in sows and respiratory distress in pigs of all ages, leading to major economic losses. To date, there are still no effective strategies to prevent and control PRRSV. Antibody-dependent enhancement (ADE), a phenomenon in which preexisting non-neutralizing antibodies or sub-neutralizing antibodies facilitate virus entry and replication, may be a significant obstacle in the development of effective vaccines for many viruses, including PRRSV. However, the contribution of ADE to PRRSV infection remains controversial, especially in vivo. Whether attenuated PRRSV vaccines prevent or worsen subsequent disease in pigs infected by novel PRRSV strains requires more research. In the present study, in vivo experiments were conducted to evaluate ADE under different immune statuses, which were produced by waiting different lengths of time after vaccination with a commercially available attenuated highly pathogenic PRRSV (HP-PRRSV) vaccine (JXA1-R) before challenging the pigs with a novel heterologous NADC30-like strain. Results Piglets that were vaccinated before being challenged with PRRSV exhibited lower mortality rates, lower body temperatures, higher bodyweight gain, and lower viremia. These results demonstrate that vaccination with JXA1-R alleviated the clinical signs of PRRSV infection in all vaccinated groups. Conclusions The obtained data indicate that the attenuated vaccine test here provided partial protection against the NADC30-like strain HNhx. No signs of enhanced PRRSV infection were observed under the applied experimental conditions. Our results provide some insight into the molecular mechanisms underlying vaccine-induced protection or enhancement in PRRSV.

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