Hog cholera

J T VAN OIRSCHOT

GENERAL INTRODUCTION: FLAVIVIRIDAE

Introduction

Hog cholera (HC) is a highly contagious viral disease of pigs that can run an acute, subacute, chronic, late onset or clinically inapparent course. The most typical feature of HC is that it is so atypical. Mortality figures vary from nil to almost 100 per cent. The interplay between viral and host factors largely determines the course and outcome of the infection. Under natural conditions, the domestic pig and the wild boar (Sus scrofa ferus) are the only animal species susceptible to infection with HC virus (HCV).

The first presumptive HC outbreaks were reported from Tennessee and Ohio in the USA in the early nineteenth century, whereas HCV first appeared in Europe in the middle of that century. Although the infection was first reported in South Africa in 1900,¹³ the country has been free of the disease since 1918. In 1903, De Schweinetz and Dorset showed that HC is caused by a filtrable agent.¹⁷

Hog cholera is classified by the Office International des Epizooties as a list A disease⁵⁹ because it is a highly devastating disease that jeopardizes international trade of pigs and pig products, and leads to substantial economic losses for the industry. The disease is prevalent in Europe, Asia and South America. The African continent is free, except for Madagascar. Many countries, such as the USA, Canada, and various European countries, have eradicated the virus, while others have stringent eradication programmes in force. Nevertheless, HCV still gave rise to many outbreaks in Europe in the 1990s. Severe outbreaks plagued Belgium and Germany in 1994. An epidemic in the Netherlands in 1997 resulted in the destruction of a total of 11 million pigs and an estimated loss of two billion US dollars.

Aetiology

Hog cholera virus belongs to the family Flaviviridae, and the genus Pestivirus. The two other members of this genus are: bovine viral diarrhoea virus (BVDV) and border disease virus (BDV). Hog cholera virus has an RNA genome that is contained in a capsid of about 28 nm in diameter, which in turn is surrounded by an envelope. Fringe-like projections of 6 to 8 nm have been demonstrated on the virion surface. The virion measures between 40 and 50 nm in diameter.

The single-stranded linear RNA genome is infective and encompasses about 12,3 kilobases. There is one open reading frame that encodes one large polyprotein of 3 898 amino acids that is cleaved by proteases to yield mature viral proteins. ^{50, 54} The open reading frame is flanked by a 5’ noncoding region of almost 400 nucleotides and a 3’ non-coding region of about 200 nucleotides. The order of the gene products is as follows:

NH₂-(N^pro-C-E^rns-E1-E2-p7-NS2.3-NS4A-NS4B-NS5ANS5B)- COOH

The left part of the genome codes for the capsid (C) protein, and the three envelope glycoproteins Erns, E1 and E2. The Erns protein has RNase activity,^{31, 66} which is unique among virus proteins, and is immunosuppressive in vitro.⁵ The E1 protein resides as a disulfide-linked E1-E2 heterodimer in the viral envelope, and the E2 also forms a disulfide-linked homodimer. The E2 is the most immunodominant protein and is composed of two independently formed antigenic domains.⁹⁰ The p7 protein is probably a non-structural protein. The right larger part of the genome solely codes for non-structural proteins. The NS2,3 protein is the most conserved among the pestiviruses.

Hog cholera virus can be differentiated from BVDV and BDV on the basis of differences found in the 5’ non-coding region, the E2 gene and a non-structural protein.^{28, 34, 91, 94, 102} Although HCV is genetically more stable than BVDV, its strains have been divided into two groups on the basis of differences in nucleotide sequences of the 5’ non-coding region, the N-terminal part of E2 and a region of NS5B.^{41, 95, 97} Subgroups within groups 1 and 2 have also been distinguished.^26,41 The amino acid similarity between HCV and BVDV is about 70 per cent, indicating that HCV shares a common evolutionary history with BVDV.⁶⁰ The highest degree of homology exists between the NS3 part of the non-structural NS2,3 protein, the lowest between the E2 sequences. Antigenically, there is a close relationship of HCV with the other two pestiviruses, as can be demonstrated by various serological methods, but a clear distinction can still be made. Antigenic variation, as demonstrated by the use of monoclonal antibodies (MAbs), exists among HCV strains, but all HCV strains belong to one antigenic group.^{20, 21, 100, 101}

The resistance of HCV to physical and chemical treatment is partly dependent on the strain of the virus and the material that contains the virus. For instance, in cell culture fluid virus was inactivated in 10 minutes at 60 °C,³⁸ whereas it was not inactivated in defibrinated blood at 68 °C for 30 minutes.⁷⁹ The viral infectivity is quickly destroyed below pH 4 and above pH 11, although the inactivation rate below pH 5 is dependent on the temperature: at pH 4 a half-life of 260 hours was found at 4 °C and 11 hours at 21 °C.¹⁴ Solvents such as chloroform and ether rapidly inactivate HCV, because its envelope contains lipids. The virus can remain infectious in pork and pork products for months, whereas in most environments outside the host or its tissues it is usually no longer infectious after a few days. However, in liquid pig manure the virus may survive for weeks.²⁵ For disinfection, 1 to 2...