Xishan Biology

Introduction to Pathogens

Porcine circovirus

Porcine circovirus infection is a novel infectious disease in pigs caused by Porcine circovirus (PCV). Its clinical manifestations are highly diverse, with the main characteristics including decreased physical condition, emaciation, anemia, jaundice, poor growth and development, diarrhea, respiratory distress, reproductive disorders in sows, and extensive pathological changes affecting internal organs and the skin—particularly pronounced swelling, hemorrhaging, and necrosis of the kidneys, spleen, and systemic lymph nodes. Moreover, this disease can lead to severe immunosuppression within pig populations, making them more susceptible to secondary or concurrent infections.

Pathology

 

Porcine circovirus is a non-enveloped, icosahedral DNA virus measuring 17–22 nm in diameter, making it one of the smallest animal viruses known to date. It has three genotypes: PCV1, PCV2, and PCV3. In 2016, laboratories at Huazhong Agricultural University confirmed the presence of PCV3 in China. Notably, PCV1 is non-pathogenic and can be widely detected in various tissues and organs of healthy pigs. In contrast, PCV3 has been linked to cardiac and multi-systemic inflammation, Porcine Respiratory Disease Complex (PRDC), Porcine Dermatitis and Nephropathy Syndrome (PDNS), and reproductive disorders. Among these, PCV2 poses the most severe threat in commercial pig production, as it is closely associated with the recently emerged post-weaning multisystemic wasting syndrome (PMWS). This disease has caused significant economic losses to the global swine industry due to its rapid spread and devastating impact. Remarkably, PCV2 exhibits remarkable stability under typical farming conditions, even thriving in highly acidic environments with a pH as low as 3. Moreover, PCV2 remains infectious after surviving exposure to temperatures as high as 56°C for extended periods, while it can still survive for up to 15 minutes at 70°C. Interestingly, PCV2 can persist for as long as six months in fecal matter, retaining its infectivity throughout this time.

Epidemiology

 

Pigs are the primary hosts of PCV. They exhibit a high susceptibility to PCV, with pigs of all ages being susceptible to infection—but piglets often develop severe clinical signs upon infection. In Germany and Canada, the prevalence of PCV antibodies in pig populations reaches as high as 95% and 55%, respectively. In the UK and Ireland, antibody positivity rates are even higher, at 86% and 92%, though not all infected animals necessarily show symptoms of PMWS. In China, serological surveys conducted in selected provinces and cities revealed that among 20-day-old weaned piglets, the positive rate was 0%; for 1- to 2-month-old weaned piglets, the rate rose to 16.5%. Among gilts, the positive rate was 42.3%, while in multiparous sows, it climbed to 85.6%. Meanwhile, in growing-finishing pigs, the positive rate stood at 51%, resulting in an overall positive rate of 42.9% across all age groups. Clinically, symptoms may persist for several months, peaking between 6 and 12 months before gradually declining. Notably, there can be significant variation in infection rates between different pig groups. This is because maternal PCV antibodies, initially present in nursing piglets, begin to wane around 8 to 9 weeks after birth. However, when these young pigs are transferred to finishing pens (at approximately 11 to 13 weeks of age), they are re-exposed to PCV, leading to a resurgence of PCV antibodies. Infected pigs can shed the virus through nasal secretions, feces, and other waste products, facilitating transmission via both the digestive and respiratory routes.

Clinical symptoms and pathological changes

 

PCV 2 infection can cause a variety of the following conditions:

PMWS: Typically affects weaned piglets, presenting symptoms such as poor mental state, reduced appetite, slightly elevated body temperature, muscle weakness and atrophy, diarrhea, respiratory distress, eyelid swelling, jaundice, anemia, emaciation, and stunted growth—often resulting in significant weight discrepancies compared to pigs of the same age. Affected pigs may also develop skin eczema and exhibit generalized lymph node lesions, particularly prominent swelling in the inguinal, mesenteric, bronchial, and mediastinal lymph nodes. Recovered pigs often become "stiff pigs." Post-mortem examination reveals enlarged lymph nodes, liver cirrhosis, and multifocal mucopurulent bronchitis. The lungs show signs of atrophy, appearing grayish to brownish with a mottled pattern and feeling rubbery to the touch. The spleen is enlarged and exhibits necrotic areas. The kidneys are pale, swollen, and marked by necrotic foci. Additionally, pericarditis, pleural effusion accompanied by fibrinous exudates, and hemorrhagic or necrotic lesions on the gastric and intestinal mucosa are commonly observed.
PDNS: Typically affects pigs between 8 and 18 weeks of age, characterized primarily by irregular, reddish-purple, raised lesions on the perineal region and skin of the limbs. Affected pigs exhibit subcutaneous edema, loss of appetite, and sometimes an elevated body temperature. Most cases result in death within 3 days, though in some instances, the disease may persist for 2 to 3 weeks. Post-mortem examination reveals enlarged, pale kidneys with pinpoint hemorrhages or necrotic areas. Histological findings include hemorrhagic necrotizing dermatitis and arteritis, as well as exudative glomerulonephritis and interstitial nephritis.

Reproductive Disorders: Both PCV1 and PCV2 infections can lead to reproductive disorders, resulting in increased estrus recurrence rates in sows, mummified fetuses, miscarriages, as well as stillbirths and the birth of weak piglets. Among these, reproductive issues caused by PCV2 are more severe.

The Impact on Research

 

Changes in lymphoid tissues following natural or experimental infection: In pigs infected with PCV 2, characteristic microscopic lesions were observed in the lymphoid tissues, including multifocal and even diffuse infiltration of histiocytes and polymorphic giant cells. Additionally, both the germinal centers and paracortical regions of lymphoid follicles exhibited marked depletion of lymphocytes. The extent of lymphocyte depletion was closely correlated with the viral load in the tissues—higher viral loads were associated with more severe lymphocytic loss. Shibahara et al. conducted histopathological analyses of lymphoid organs from pigs naturally infected with PCV 2, revealing that PCV 2 infection induces apoptosis of B lymphocytes (CD-79a), leading to a significant reduction in B-cell populations and subsequently impairing the body's humoral immune response. It is precisely because PCV 2 infection can cause damage to lymphoid tissues that researchers have begun to suspect the virus may possess immunosuppressive properties.

PCV 2 natural infection leads to changes in peripheral blood lymphocyte subsets in pigs. Segales et al. and Darwich et al., using flow cytometry, investigated peripheral blood mononuclear cells (PBMCs) from pigs naturally infected with PCV 2 and found that, compared to healthy control groups uninfected by PCV 2, pigs naturally infected with PCV 2 exhibited significant alterations in peripheral blood leukocyte subsets: monocytes were markedly increased, while the numbers of T cells (primarily CD4+) and B lymphocytes declined. Additionally, the proportion of IgM-producing cells also decreased. Notably, CD8 cell counts dropped, leading to a significant reduction in the CD4/CD8 ratio. Furthermore, low-density, immature granulocytes appeared in the bloodstream. Since both CD8 cells and CD4+/CD8 double-positive (DP) cells play crucial roles in the immune system—where CD8 cells are particularly associated with cellular immune responses, and DP cells possess dual functions as both immune memory cells and effector lymphocytes—it is reasonable to conclude that their depletion would inevitably impair the body's overall immune response.

Prevention and Removal

 

Vaccination is the most effective and cost-efficient method for controlling circovirus disease. Additionally, regular monitoring is essential. While antibody tests cannot distinguish between different types of circovirus infections, a positive result from PCR testing conducted on samples such as blood, lymph nodes, lungs, or kidneys taken from affected pigs can confirm the diagnosis. Currently, there are several types of circovirus vaccines available: 1. **Inactivated Whole-Virus Vaccines**: These vaccines provide excellent immune responses, are easy to store, but come with higher production costs. The vaccine strains primarily include PCV 2a and PCV 2b; however, their protective efficacy against the currently prevalent PCV 2d strain still requires evaluation. 2. **Chimeric Inactivated Vaccines**: These vaccines are designed by using PCV 1 as a backbone, with its ORF2 sequence replaced by the ORF2 sequence from PCV 2, followed by viral rescue techniques to generate a recombinant attenuated strain (PCV 1-2). Alternatively, PCV 2 can serve as the backbone, with its ORF2 sequence swapped out for that of PCV 1, producing another recombinant attenuated strain (PCV 2-1). Both chimeric strains demonstrate strong immunogenicity, effectively stimulating the body to produce robust PCV 2-specific antibodies. 3. **Subunit Vaccines**: These vaccines utilize advanced genetic engineering methods—such as baculovirus expression systems, yeast-based systems, or E. coli expression systems—to efficiently produce the PCV 2 Cap protein. After high-density fermentation, the Cap protein is extracted, purified, and inactivated. It is then emulsified with an appropriate adjuvant to formulate the final vaccine. Notably, subunit vaccines contain no viral nucleic acids, making them highly amenable to thorough purification—a key advantage that positions them as the current mainstream approach in circovirus vaccine development.

Regularly adding antibiotic drugs such as Tylan, Chlortetracycline, and Amoxicillin to feed can help prevent this disease or reduce its incidence, primarily by suppressing common bacterial pathogens in the pig herd and enhancing the pigs' overall resistance. For pigs already affected, it's best to cull them; for those that cannot be culled, combining the aforementioned antibiotics with symptomatic treatments can effectively lower the mortality rate. At the same time, it’s crucial to strengthen shoulder and neck disinfection as well as improve feeding management practices to minimize stress in piglets, while also implementing comprehensive control measures against other infectious diseases. Inside pig houses, silver ammonia solution should be used for disinfection every 10 days, with regular spraying of "Hu She An." Meanwhile, the external environment should be disinfected periodically using caustic soda or potassium peroxymonosulfate complexes.

References

 

1. Investigation on the Prevalence of Porcine Circovirus Type 2 Infection and Immune Efficacy in the Suzhong Region. Yan Yourong; Fang Xianghong; Wei Ning; Xiao Ning. Modern Animal Husbandry and Veterinary Medicine, 2021

2. Genome Sequencing and Genetic Evolution Analysis of Porcine Circovirus Type 1 from Five Hunan Pig Strains. He Shicheng; Wang Ziw ei; Wang Cheng; Hu Qiaoyun; Tang Xiaoming; Wang Weiguo; Xie Yiling; Wang Changjian. Chinese Journal of Animal Quarantine, 2021

3. Investigation on the Status of Porcine Circovirus Infection in Diseased Pigs and Slaughtered Pig Herds in Selected Areas of Hunan Province. He Shicheng; Wang Ziw ei; Ding Chaoyang; Hu Qiaoyun; Tang Xiaoming; Wang Weiguo; Liu Daoxin; Xie Yiling; Wang Changjian. China Animal Quarantine, 2021

4. Research Progress in Diagnostic Techniques for Porcine Circovirus Type 2 Infection. Deng Qixia; Lü Qizhuang; Zhang Qi; Zhuo Yanling; Deng Jiahua. Northeast Agricultural Science, 2021

5. Establishment and Application of Digital Microdroplet PCR Technology for Porcine Circovirus Type 2 Detection. Wu Mengchen; Jin Chenchen; He Yongqiang; Zeng Ruoxue; Chen Xiaojin; Cheng Changyong; Shuai Jiangbing; Dong Zhizhen; Song Houhui; Yu Xiaoping; Zhang Xiaofeng. Chinese Journal of Preventive Veterinary Medicine, 2021

6. PCV2 Detection and Genetic Variation Analysis in Slaughtered Pigs from Shaanxi Province. Luo Bihao; Xu Hao; Luo Lihua; Fan Yuxin; Yang Zhuolin; Wang Yuting; Ji Tianrun; Kang Yukun; Han Xueying; Guo Kangkang. Animal Husbandry & Veterinary Medicine, 2021

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