Etienne Thiry

The order Herpesvirales

The taxonomy of herpesviruses has been updated by the International Committee on Taxonomy of Viruses (ICTV). The former family Herpesviridae has been split into three families, which have been incorporated into the new order Herpesvirales. The revised family Herpesviridae retains the mammal, bird and reptile viruses, the new family Alloherpesviridae incorporates the fish and frog viruses, and the new family Malacoherpesviridae contains a bivalve virus. Three new genera have been created in the family Herpesviridae, namely Proboscivirus in the subfamily Betaherpesvirinae and Macavirus and Percavirus in the subfamily Gammaherpesvirinae. These genera have been formed by the transfer of species from established genera and the erection of new species, and other new species have been added to some of the established genera. In addition, the names of some nonhuman primate virus species have been changed. The family Alloherpesviridae has been populated by transfer of the genus Ictalurivirus and addition of the new species Cyprinid herpesvirus 3. The family Malacoherpesviridae incorporates the new genus Ostreavirus containing the new species Ostreid herpesvirus 1.

Feline Herpesvirus Infection: ABCD Guidelines on Prevention and Management:

Overview Feline viral rhinotracheitis, caused by feline herpesvirus (FHV), is an upper respiratory tract disease that is often associated with feline calicivirus and bacteria. In most cats, FHV remains latent after recovery, and they become lifelong virus carriers. Stress or corticosteroid treatment may lead to virus reactivation and shedding in oronasal and conjunctival secretions. Infection Sick cats shed FHV in oral, nasal and conjunctival secretions; shedding may last for 3 weeks. Infection requires direct contact with a shedding cat. Disease signs Feline herpesvirus infections cause acute rhinitis and conjunctivitis, usually accompanied by fever, depression and anorexia. Affected cats may also develop typical ulcerative, dendritic keratitis. Diagnosis Samples consist of conjunctival, corneal or oropharyngeal swabs, corneal scrapings or biopsies. It is not recommended that cats recently vaccinated with a modified-live virus vaccine are sampled. Positive PCR results should be interpreted with caution, as they may be produced by low-level shedding or viral latency. Disease management ‘Tender loving care’ from the owner, supportive therapy and good nursing are essential. Anorexic cats should be fed blended, highly palatable food - warmed up if required. Mucolytic drugs (eg, bromhexine) or nebulisation with saline may offer relief. Broad-spectrum antibiotics should be given to prevent secondary bacterial infections. Topical antiviral drugs may be used for the treatment of acute FHV ocular disease. The virus is labile and susceptible to most disinfectants, antiseptics and detergents.

Feline immunodeficiency. ABCD guidelines on prevention and management.

Overview Feline immunodeficiency virus (FIV) is a retrovirus closely related to human immunodeficiency virus. Most felids are susceptible to FIV, but humans are not. Feline immunodeficiency virus is endemic in domestic cat populations worldwide. The virus loses infectivity quickly outside the host and is susceptible to all disinfectants. Infection Feline immunodeficiency virus is transmitted via bites. The risk of transmission is low in households with socially well-adapted cats. Transmission from mother to kittens may occur, especially if the queen is undergoing an acute infection. Cats with FIV are persistently infected in spite of their ability to mount antibody and cell-mediated immune responses. Disease signs Infected cats generally remain free of clinical signs for several years, and some cats never develop disease, depending on the infecting isolate. Most clinical signs are the consequence of immunodeficiency and secondary infection. Typical manifestations are chronic gingivostomatitis, chronic rhinitis, lymphadenopathy, weight loss and immune-mediated glomerulonephritis. Diagnosis Positive in-practice ELISA results obtained in a low-prevalence or low-risk population should always be confirmed by a laboratory. Western blot is the ‘gold standard’ laboratory test for FIV serology. PCR-based assays vary in performance. Disease management Cats should never be euthanased solely on the basis of an FIV-positive test result. Cats infected with FIV may live as long as uninfected cats, with appropriate management. Asymptomatic FIV-infected cats should be neutered to avoid fighting and virus transmission. Infected cats should receive regular veterinary health checks. They can be housed in the same ward as other patients, but should be kept in individual cages.

Feline Infectious Peritonitis ABCD Guidelines on Prevention and Management

Overview Feline Coronavirus infection is ubiquitous in domestic cats, and is particularly common where conditions are crowded. While most FCoV-infected cats are healthy or display only a mild enteritis, some go on to develop feline infectious peritonitis, a disease that is especially common in young cats and multi-cat environments. Up to 12% of FCoV-infected cats may succumb to FIP, with stress predisposing to the development of disease. Disease signs The ‘wet’ or effusive form, characterised by polyserositis (abdominal and/or thoracic effusion) and vasculitis, and the ‘dry’ or non-effusive form (pyogranulomatous lesions in organs) reflect clinical extremes of a continuum. The clinical picture of FIP is highly variable, depending on the distribution of the vasculitis and pyogranulomatous lesions. Fever refractory to antibiotics, lethargy, anorexia and weight loss are common non-specific signs. Ascites is the most obvious manifestation of the effusive form. Diagnosis The aetiological diagnosis of FIP ante-mortem may be difficult, if not impossible. The background of the cat, its history, the clinical signs, laboratory changes, antibody titres and effusion analysis should all be used to help in decisionmaking about further diagnostic procedures. At the time of writing, there is no non-invasive confirmatory test available for cats without effusion. Disease management In most cases FIP is fatal. Supportive treatment is aimed at suppressing the inflammatory and detrimental immune response. However, there are no controlled studies to prove any beneficial effect of corticosteroids.

Comparative pathogenesis of acute and latent infections of calves with bovine herpesvirus types 1 and 5

Summary. This study was conducted to compare the pathogenesis of acute and latent infections with closely related bovine herpesvirus types 1 (BHV-1) and 5 (BHV-5) in their natural host. Two groups of eight calves were inoculated intranasally with BHV-1 or BHV-5. Although BHV-1 and BHV-5 similarly replicate in the nasal mucosa after inoculation, both viruses differ markedly in their ability to cause disease, BHV-5 being responsible of some fatal encephalitis while BHV-1 inducing rhinotracheitis. Virus isolation and immunohistochemistry demonstrated that BHV-5 replicates extensively in neurons of the central nervous system (CNS) and in respiratory cells of lungs, tracheal and nasal mucosae. Invasion of the CNS likely occurs through the trigeminal and olfactory pathways. Both groups developed cross-neutralising antibodies during this experiment suggesting partial clinical cross-protection afforded by the two infections. Three months after primary infection, experimental reactivation showed that BHV-5 was able to establish latency in the trigeminal ganglia but also the CNS of surviving calves. Moreover, laboratory findings suggested that BHV-5 could also persist in the tracheal and nasal mucosae. These results indicate that, after primary infection, BHV-1 and BHV-5 displayed similar biological features and consequently need to be considered together for the control of BHV-1 infection.

Feline Leukaemia: ABCD Guidelines on Prevention and Management

Overview Feline leukaemia virus (FeLV) is a retrovirus that may induce depression of the immune system, anaemia and/or lymphoma. Over the past 25 years, the prevalence of FeLV infection has decreased considerably, thanks both to reliable tests for the identification of viraemic carriers and to effective vaccines. Infection Transmission between cats occurs mainly through friendly contacts, but also through biting. In large groups of non-vaccinated cats, around 30–40% will develop persistent viraemia, 30–40% show transient viraemia and 20–30% seroconvert. Young kittens are especially susceptible to FeLV infection. Disease signs The most common signs of persistent FeLV viraemia are immune suppression, anaemia and lymphoma. Less common signs are immune-mediated disease, chronic enteritis, reproductive disorders and peripheral neuropathies. Most persistently viraemic cats die within 2–3 years. Diagnosis In low-prevalence areas there may be a risk of false-positive results; a doubtful positive test result in a healthy cat should therefore be confirmed, preferably by PCR for provirus. Asymptomatic FeLV-positive cats should be retested. Disease management Supportive therapy and good nursing care are required. Secondary infections should be treated promptly. Cats infected with FeLV should remain indoors. Vaccination against common pathogens should be maintained. Inactivated vaccines are recommended. The virus does not survive for long outside the host.

Virulence, immunogenicity and reactivation of bovine herpesvirus 1 mutants with a deletion in the gC, gG, gI, gE, or in both the gI and gE gene

Within the framework of developing a marker vaccine against bovine herpesvirus 1 (BHV1), several mutants with deletions in non-essential glycoprotein genes were constructed. Glycoprotein gC, gG, gI and gE single deletion mutants, a gI/gE double deletion mutant and a gE frame-shift mutant were made. The virulence and immunogenicity of these mutants were evaluated in specific-pathogen-free calves. Except for the gC deletion mutant, all mutants were significantly less virulent than the parental wild-type (wt) BHV1 strain Lam. The virulence of the gI and the gI-/gE- mutants was almost completely reduced. Upon challenge infection, the calves of the control group became severely ill, whereas all other calves remained healthy. The reduction of the virus shedding after challenge infection was related to the virulence of the strain of primary inoculation. Virus shedding was almost completely reduced in calves first inoculated with Lam-wt or with gC- and the least reduced in calves inoculated with gI- or gI-/gE-. Six weeks after challenge, all calves were treated with dexamethasone to study whether mutant or challenge virus or both could be reactivated. The gC- and the gG- mutants were reactivated, whereas none of the other mutants were reisolated. Reactivation of challenge virus was reduced in all calves inoculated with mutant viruses. The gC deletion mutant was too virulent and the gI and the gI/gE deletion mutants were the least immunogenic, but based on residual virulence and immunogenicity, both the gG and the gE deletion mutants are candidates for incorporation in live BHV1 vaccines. However, it also depends on the kinetics of the anti-gG and anti-gE antibody response after wild-type virus infection, whether these deletion mutants are really suitable to be incorporated in a marker vaccine.

Genetic relationships between bovine herpesvirus 4 and the gammaherpesviruses epstein-Barr virus and herpesvirus saimiri

The overall arrangement of genes in the unique central part of the bovine herpesvirus type 4 (BHV-4) genome has been deduced by analysis of short DNA sequences. Twenty-three genes conserved in at least one of the completely sequenced herpesviruses have been identified and localized. All of these genes encoded amino acid sequences with higher similarity to proteins of the gammaherpesviruses Epstein-Barr virus (EBV) and herpesvirus saimiri (HVS) than to the homologous products of the alphaherpesviruses varicella-zoster virus and herpes simplex virus type 1 or the betaherpesvirus human cytomegalovirus. The genome organization of BHV-4 had also an overall colinearity with that of the gammaherpesviruses EBV and HVS. Furthermore, the BHV-4 genes content and arrangement were more similar to those of HVS than to those of EBV, suggesting that BHV-4 and HVS are evolutionarily more closely related to each other than either are to EBV. BHV-4 DNA sequences were generally deficient in CpG dinucleotide. This CpG deficiency is characteristic of gammaherpesvirus genomes and suggests that the BHV-4 latent genome is extensively methylated. Despite several biological features similar to those of betaherpesviruses, BHV-4 displays the molecular characteristics of the representative members of the gammaherpesvirinae subfamily.

Bluetongue in Belgium, 2006.

Bluetongue has emerged recently in Belgium. A bluetongue virus strain was isolated and characterized as serotype 8. Two new real-time reverse transcription–quantitative PCRs (RT-qPCRs) that amplified 2 different segments of bluetongue virus detected this exotic strain. These 2 RT-qPCRs detected infection earlier than a competitive ELISA for antibody detection.

Novel norovirus recombinants and GII.4 sub-lineages associated with outbreaks between 2006 and 2010 in Belgium

BackgroundNoroviruses (NoVs) are an important cause of acute gastroenteritis in humans worldwide. To gain insight into the epidemiologic patterns of NoV outbreaks and to determine the genetic variation of NoVs strains circulating in Belgium, stool samples originating from patients infected with NoVs in foodborne outbreak investigations were analysed between December 2006 and December 2010.ResultsNoVs were found responsible of 11.8% of all suspected foodborne outbreaks reported in the last 4 years and the number of NoV outbreaks reported increased along the years representing more than 30% of all foodborne outbreaks in 2010. Genogroup II outbreaks largely predominated and represented more than 90% of all outbreaks. Phylogenetic analyses were performed with 63 NoV-positive samples for the partial polymerase (N = 45) and/or capsid gene (N = 35) sequences. For 12 samples, sequences covering the ORF1-ORF2 junction were obtained. A variety of genotypes was found among genogroups I and II; GII.4 was predominant followed in order of importance by GII.2, GII.7, GII.13, GI.4 and GI.7. In the study period, GII.4 NoVs variants 2006a, 2006b, 2007, 2008 and 2010 were identified. Moreover, phylogenetic analyses identified different recombinant NoV strains that were further characterised as intergenotype (GII.e/GII.4 2007, GII.e/GII.3 and GII.g/GII.1) and intersub-genotype (GII.4 2006b/GII.4 2007 and GII.4 2010/GII.4 2010b) recombinants.ConclusionsNoVs circulating in the last 4 years in Belgium showed remarkable genetic diversity either by small-scale mutations or genetic recombination. In this period, GII.4 2006b was successfully displaced by the GII.4 2010 subtype, and previously reported epidemic GII.b recombinants seemed to have been superseded by GII.e recombinants in 2009 and GII.g recombinants in 2010. This study showed that the emergence of novel GII.4 variants together with novel GII recombinants could lead to an explosion in NoV outbreaks, likewise to what was observed in 2008 and 2010. Among recombinants detected in this study, two hitherto unreported strains GII.e/GII.3 and GII.g/GII.1 were characterised. Surveillance will remain important to monitor contemporaneously circulating strains in order to adapt preventive and curative strategies.