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Porcine respiratory coronavirus infection

Porcine respiratory coronavirus infection

Porcine respiratory coronavirus infection

Previous Authors: K VAN REETH AND M B PENSAERT

Current Authors:
A N VLASOVA - Assistant Professor, PhD, DVM, The Ohio State University, 1680 Madison Ave, Wooster, Ohio, OH 44691, USA 
S N LANGEL - Graduate Research Assistant, MS, PhD Candidate, The Ohio State University, 1680 Madison Avenue, Wooster, Ohio, OH 44691, USA
L J SAIF - Professor, MS, PhD, Food Animal Health Research Program, CFAES and CVM, OARDC, Ohio State University, 1680 Madison Ave, Wooster, Ohio, OH 44691, USA

GENERAL INTRODUCTION: CORONAVIRIDAE

Introduction

A new virus antigenically closely related to transmissible gastroenteritis virus (TGEV), appeared in 1984 in pigs in Belgium and rapidly spread to all other European countries, becoming endemic even in TGEV-free countries. In 1989, the virus was detected in two herds in the US with no history of TGEV vaccination or clinical disease.12, 32 Unlike TGEV, this virus does not cause an enteropathogenic infection but replicates to high levels in the respiratory tract of piglets. The virus was therefore designated porcine respiratory coronavirus (PRCV).20

Porcine respiratory coronavirus is generally considered non-pathogenic because the infection on pig farms is mostly subclinical. However, when complicated by secondary (unknown) agents, PRCV contributes to multifactorial respiratory disease in the field.2

Aetiology

PRCV is a naturally occurring deletion mutant of TGEV, with deletions in ORF 3 and the gene encoding the S glycoprotein.22. This S gene deletion resulted in the absence of some N-terminal epitopes in PRCV S glycoprotein that induce non-neutralizing antibodies against TGEV.4 It is apparent that PRCV is not a TGEV vaccine strain, as all vaccine strains so far examined have the intact TGEV S glycoprotein epitopes. The PRCV virions have the typical morphology of coronaviruses. PRCV induces antibodies that cross-neutralize TGEV infectivity and vice versa.

The virus can be cultured in primary pig kidney cells, producing discrete cytopathic effects. Porcine kidney (PD5) and swine testis (ST) cell lines are most suitable for PRCV propagation that cause marked cytopathic effects, notably the formation of large syncytia and the destruction of the monolayer.

Epidemiology

Transmission of PRCV occurs by direct contact with infected animals or by aerosols. There is no evidence for faecal-oral transmission of PRCV. Airborne transmission occurs readily in regions with high pig density and is responsible for infection of high-health-status herds and virus transmission between farms situated several kilometres apart.

After its first appearance in Belgium in 1984, PRCV spread rapidly and extensively in Western Europe. It had become endemic within a two-and-a-half-year period in most pig-raising countries, such as France, the UK, Germany, the Netherlands, Spain and Denmark.

In serosurveys in Belgium, nearly 100 per cent of pig herds were positive for PRCV antibodies from 1990 until 1999. Serological studies on closed breeding and breeding–fattening farms have demonstrated that the virus can persist in pig herds.21 Virus persists in closed breeding farms  by regularly infecting newly weaned pigs, even in the presence of maternal antibodies.21 PRCV can persist in the herd throughout the year, temporarily disappearing in summer and reappearing in the nursing and fattening pigs during the cold season. Coincident with the widespread dissemination of PRCV, the seroprevalence of TGEV in Europe has decreased substantially.3, 21 (see Transmissible gastroenteritis).

In the USA, PRCV was first isolated in 1989.32 For unknown reasons, it did not spread as rapidly initially in the swine population of the USA as it did in Western Europe. A small-scale serological survey in Iowa — in which 16 of the 22 herds tested were PRCV positive — revealed that the prevalence of PRCV in the mid-western states may be on the rise.33 Porcine respiratory coronavirus has also been isolated in Korea and Japan.6, 15, 25

Pathogenesis

Experimental infection studies have shown that PRCV replicates readily in epithelial cells of the nasal mucosa, tonsils and lungs.8, 19 Viraemia was only confirmed in very young pigs (less than one week old), whereas their parenchymal organs and lymph nodes were virus-negative in immunofluorescence studies. Large amounts of PRCV are isolated from the lungs (107,5 to 108,3 TCID50/g tissue) and from nasal swabs (106,5 to 107,3 TCID50/100 mg secretion) during the first week after inoculation.8, 26, 29 PRCV antigens are detected in several types of lung cells such as the epithelial cells of bronchi and bronchioli, in alveoli and in macrophages in the alveolar septa and spaces8,19,24.In studies with Belgian PRCV isolates, cells of the alveolar epithelia and septa were predominantly infected, while USA isolates were reported to replicate mainly in bronchiolar epithelial cells.8, 24 Nasal virus excretion continues for eight to nine days after inoculation, suggesting a similar duration of virus replication in the lungs.1, 17, 29 Virus neutralizing antibodies in serum are detectable by 10 to 14 days after infection.17, 30

Even after direct virus inoculation into the intestinal lumen, PRCV replicates only to a very limited extent in the small intestine in a few cells located in or underneath the epithelium of the intestinal villi and crypts.8, 9 This is different from TGE, in which nearly all enterocytes of the small intestine are infected.

Clinical signs

Porcine respiratory coronavirus infection on pig farms is subclinical. However it is associated with respiratory disease problems in conjunction with porcine reproductive and respiratory syndrome virus and several bacteria, such as Haemophilus parasuis, Streptococcus suis and Pasteurella multocida.11, 13, 14, 15

In experimental infections, both European and USA PRCV isolates have failed to induce clinical disease when gnotobiotic pigs were used.8, 11, 19, 32 Only in a few studies in which conventional or specific-pathogen free pigs were infected, were mild dyspnoea and polypnoea and/or a short lasting fever manifested.1, 10, 17, 30 Slightly reduced weight gain was recorded in some of these studies.12

Several studies were conducted to test the hypotheses that the severity of disease induced by PRCV depends on concurrent infection or may be aggravated by corticosteroid treatment. The clinical effects of dual virus infections with PRCV and either influenza virus or porcine reproductive and respiratory syndrome virus were more severe than were those during single virus infections in some, but not in all, studies.14, 17, 27, 29 In addition, the severity of the clinical syndrome of these dual virus infections was highly variable. Combined inoculations with PRCV and bacterial endotoxin, on the other hand, invariably resulted in  prominent laboured breathing and lethargy in all pigs, while single agent inoculations were subclinical.28 These data may be of particular relevance with regard to the field situation because airborne endotoxin occurs in respirable dust in swine buildings. Furthermore, high concentrations of endotoxins are released in the lungs during Gram-negative bacterial infections, which often occur secondary to virus infections of the lungs. Finally, corticosteroid (dexamethasone) treatment of conventional pigs resulted in immunosuppression that led to sneezing, coughing, mild fever, mild polypnoea likely following PRCV infection.13

Pathology

Macroscopic and microscopic lung lesions are consistently observed in pigs after experimental infection with PRCV.8, 10, 11, 13, 14, 19, 26 Gross pulmonary consolidation may involve up to 30 to 60 per cent of the lungs, even in asymptomatic pigs. Differences in the extent of lung pathology induced by various USA PRCV isolates have been demonstrated that might relate to different genome deletions.10 Histologically, there is mild to moderate interstitial pneumonia and bronchiolitis, manifested by septal infiltrations of mononuclear cells and small numbers of neutrophils, the presence of a bronchiolar and alveolar lymphohistiocytic exudate, and occasional epithelial cell necrosis. The regeneration process of the lung starts after approximately one week.19

Diagnosis

The diagnosis of PRCV infection can be achieved by isolation of the virus from nasopharyngeal swabs or lung-tissue homogenates in cell culture and by PRCV RNA detection using RT-PCR or real-time RT-PCR. The existing RT-PCR assays allow differentiation of TGEV and PRCV.7, 16

After experimental infection, PRCV antigens can be demonstrated by immunofluorescence in frozen sections of lung tissue and in smears of nasal cells.8, 13, 14, 18

The serodiagnosis of PRCV infection by the demonstration of neutralizing antibodies against TGEV is only presumptive for PRCV if there is no diarrhoeic disease present or history of TGE on the farm. For confirmation, the absence of antibodies directed against the differential epitope on TGEV (see Aetiology) must be demonstrated by the use of a blocking ELISA. The test necessitates the use of a monoclonal antibody specific for that epitope.5

Control

Vaccines against PRCV are not available. The fact that uncomplicated PRCV infections are mostly subclinical make the cost-efficiency of PRCV vaccination questionable. Sanitary measures cannot prevent PRCV infections in pig herds, but they do reduce the risk of multifactorial respiratory disease.

It has been convincingly demonstrated that PRCV infection of sows confers partial protection to their offspring against TGEV challenge.23, 31 In countries where classical TGE is still a problem, such as the USA, PRCV exposure of sows may be useful in its control.

References

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