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SECTION 1
Viral Infections
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CHAPTER 1
HERPESVIRUS INFECTIONS
FREDERIK WIDÉN, CARLOS G. DAS NEVES, FRANCISCO RUIZ-FONS, HUGH W. REID, THIJS KUIKEN, DOLORES GAVIER-WIDÉN AND ERHARD F. KALETA
INTRODUCTION
FREDERIK WIDÉN1 AND CARLOS G. DAS NEVES2
1National Veterinary Institute (SVA) and Swedish University of Agricultural Science, Uppsala, Sweden
2Norwegian School of Veterinary Science, Department of Food Safety and Infection Biology, Section of Arctic Veterinary Medicine, Tromsø, Norway
Herpesvirales is a vast order of currently approximately 130 large enveloped DNA virus species divided into three families. Herpesviruses have been isolated from most species investigated, including mammals, birds, reptiles, insects, molluscs and amphibians; and several animal species have been found to be infected with several herpesvirus species. Herpesviruses are evolutionarily old viruses that have co-evolved with their hosts for more than 250 million years.
Morphologically, herpesviruses are distinct from all other viruses, with a linear, double-stranded DNA genome of 125–250 kbp contained within an icosadeltahedral capsid of 100 to 110 nm and containing 162 capsomers. This capsid is surrounded by an amorphous-looking, protein matrix, with variable thickness, called the tegument and then by a trilaminar envelope containing lipids and proteins, bringing the total size of the virion from 120 nm up to almost 300 nm. The presence of lipids in the envelope has practical implications, as it renders herpesviruses sensitive to detergents and lipid solvents. There are numerous spikes of glycoproteins protruding from the envelope. These spikes are more numerous and shorter than in other virus families. The variation in the size of the genome is to some extent attributed to the presence of internal and terminal repeats. Common to all herpesviruses is that they are complex and contain genes for a large number of enzymes necessary for their replication, that viral DNA synthesis and capsid formation takes place in the nucleus of the infected cell, and that infected cells are destroyed owing to the virus replication and release of virus progeny, together with the ability of herpesviruses to establish latent infections. During latency no virus progeny is produced and the genome remains in a circular form.
The order Herpesvirales can be divided into three families: the family Herpesviridae contains the viruses of mammals, birds and reptiles; the family Alloherpesviridae contains fish and frog viruses; and the family Malacoherpesviridae contains the bivalve virus. The family Herpesviridae, which includes approximately 79 known virus species so far, is further subdivided into three subfamilies: Alphaherpesvirinae, Betaherpesvirinae and Gammaherpesvirinae.
Alphaherpesviruses are characterized by a rather broad host range, short replication cycle, rapid destruction of infected cells and a rapid spread in the host. Furthermore, they have the ability to establish life-long latent infection in sensory ganglia, or sometimes in other ganglia. Alphaherpesviruses are known to cause several acute diseases of veterinary importance.
By contrast, betaherpesviruses, often called cytomegaloviruses, have a restricted host range, long replication cycle and a slow spread of infection, with latent or persistent infections possible in a range of tissues, e.g. lymphoreticular cells, secretory glands and kidneys. Infection usually results in significant enlargement of certain cell types, known as cytomegaly. Infections are often widely distributed in the host population and usually not clinically apparent, except when such a virus appears in a previously uninfected herd.
Gammaherpesviruses usually have a host range restricted to the host’s family or order. Viruses of this subfamily have specificity for either B- or T-lymphocytes and may cause lymphoproliferative disease. Latency of gammaherpesviruses may be established in lymphoid tissue. Infections with viruses from this subfamily generally cause few clinical signs in the main host but may cause severe disease in other related species, as exemplified by malignant catarrhal fever.
The ability of herpesviruses to cause latent infections is of great epidemiological importance, as it is generally not possible to determine or confirm if an animal is latently infected owing to the almost complete absence of gene expression, viral replication or host immune response during latency. Thus, diagnostic assays usually do not detect latent infections. A latent infection can, however – under certain conditions such as in the presence of concurrent disease, stress, immunosuppression or hormonal changes – reactivate, resulting in a productive infection with excretion of viral particles, transmission and infection of susceptible animals.
HERPESVIRUS INFECTIONS IN WILD MAMMALS
CARLOS G. DAS NEVES
Norwegian School of Veterinary Science, Department of Food Safety and Infection Biology, Section of Arctic Veterinary Medicine, Tromsø, Norway
It is believed that most animal species can harbour at least one, if not more, endemic herpesviruses. With more than 5000 mammalian species and only around 200 herpesviruses identified so far, one can easily speculate on the many more yet to be found and added to the order Herpesvirales, already the biggest order of viruses in existence.
Phylogenetic studies show co-speciation between herpesviruses and their hosts, with divergences in viral taxonomy mimicking those of animal species. Whereas herpesviruses of mammals and birds have shared a common ancestor, divergence seems to have happened over 220 million years ago, with speciations within sublineages in the last 80 million years as mammalian radiation took place(1,2).
Although many herpesviruses are well adapted to their natural host, there are several that can cross the species barrier and infect other animals. This is the case for many herpesviruses that can circulate between wild animals and domestic animals (e.g. Alcelaphine herpesvirus 1 and 2). Some others can have zoonotic potential, such as herpesviruses from primates that infect and cause severe disease in humans (e.g. Macacine herpesvirus 2). Human-specific herpesviruses also have the potential to infect wild animals.
Table 1.1 summarizes some of the most important herpesviruses relevant to European wildlife.
TABLE 1.1 Important mammalian herpesviruses for European wildlife. Viruses are presented according to their taxonomic distribution within the three subfamilies of the order Herpesvirales.
AUJESZKY’S DISEASE, OR PSEUDORABIES
FRANCISCO RUIZ-FONS1
1Instituto de Investigación en Recursos Cinegéticos IREC (CSIC-UCLM-JCCM), Ciudad Real, Spain
Aujeszky’s disease (AD), pseudorabies or ‘mad itch’ is a neurological/respiratory disorder that affects a wide range of animals, except humans and some primates. It is caused by porcine or suid herpesvirus type 1, also known as pseudorabies virus or Aujeszky’s disease virus (ADV), which belongs to the family Herpesviridae in the genus Varicellovirus.
AETIOLOGY
ADV is a 150–180 nm virion composed of a 145 Kb linear double-stranded DNA genome within an enveloped nucleocapsid. The 105–110 nm wide nucleocapsid is formed by different structural proteins and its envelope is a lipidic membrane composed of nine different enclosed glycoproteins used in the life cycle of the virus, immune modulation and pathogenicity.
EPIDEMIOLOGY
ADV is widely distributed in European wild boar populations (Figure 1.1)(3). Some countries, where AD has not been identified in wild boar populations, have reported pseudorabies outbreaks in dogs used in boar hunting, i.e. Austria(4,5), Belgium(6), Hungary and Slovakia(7). Several European countries where ADV has not been reported or where it was eradicated from domestic pigs have not assessed the status of ADV in their wild boar populations (e.g. Denmark, Norway, Finland or the UK). Thus, the current known distribution of ADV in European wild boar populations may not be accurate.
ADV is able to infect a wide range of mammals, including ungulates, carnivores, lagomorphs, rats and mice. Infection in mammals is usually fatal; however, in some species subclinical infection is possible(8). In suids, the only natural host species for ADV, the infection may cause disease or be subclinical.
Many European wild boar populations have had laboratory assessments for the presence of ADV or anti-ADV antibodies (Figure 1.1); however, the basic understanding of ADV epidemiology in boar is poor. Pan-European serological studies on ADV in wild boar have shown that the probability of contact with the virus increases with age. ADV causes life-long latent infection in suids and naturally infected animals remain seropositive, and potentially infective, for life. A similar viral exposure risk occurs for males and females; however, sex-related differences, with higher exposure of females to ADV, is seen in some European and North African wild boar populations (9). This may be related to behavioural differences between the sexes. Intra-group transmission is higher in all-female groups of wild boar, whereas males tend to be solitary. The probability of wild boar acquiring ADV in endemic areas also seems to be dependent on population density and the extent to which the animals aggregate(10), both of which are highly variable factors across Europe, and this gives rise to regional/local variations in prevalence. Additionally, wild boar population structure, female group size, management or predation may influence the rate of transmission of ADV within and between groups. This could be the reason for the similar viral infection risk of males and females observed in many wild boar populations in Europe. Movement of individuals between infected and susceptible wild boar groups or populations is likely to be important for virus spread.
ADV survival rate in the environment is low. Transmission by the aerosol route is also low in hot and dry weather conditions, which are unfavourable for the virus, but is enhanced if weather conditions are cool and wet.
The European wild boar is currently considered as a true ADV reservoir, because the virus can infect, replicate and be excreted...
