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[Evolution of viral diseases (author's transl)].

Biological characteristics of viruses determine their distribution in men and animals as well as their means of surviving or persisting. Taking measles as an example, we show that we are dealing with a recent phenomenon in evolution--as opposed, for instance, to those infections due to arboviruses (eg yellow fever) common in tropical regions. Survival rates are lower for highly virulent viruses (myxomatosis). Antigenmodification (influenza) or latency (herpes virus infections) allow the virus repeatedly to escape the body's immune system. The distribution and clinical appearance of the infections are influenced by environmental and particularly iatrogenic impact. Complete extirpation of infections will not be possible, only their manifestations will undergo continuous change.

Animals↗

[Myxomatosis in Tunisia: seroepidemiological study in the Monastir region (Tunisia)].

A sero-epidemiological study of myxomatosis, realized in the region of Monastir, confirmed the existence and the prevalence of the disease in its nodular form. Different strains of the myxomatosis virus were isolated and identified by gel immunodiffusion test (GID) using specific polyclonal sera. Serological analyses using complement fixation (FC) and (GID) tests allowed the detection of specific antibodies in sera from both healthy and sick animals. The results also confirmed the better sensitivity of the FC over the GID. Overall rates infection of herds and animals were 54.9% and 32.63% (p < 0.05), respectively, as revealed by serological testing. These rates increase with the size of herds. Geographic distribution of myxomatosis cases suggests that the disease first appeared in the coastal region then moved inside the Sabel area. Breeding and farming conditions, associated with deficiency in sanitary and medical measures, are at the origin of the introduction and the wide distribution of myxomatosis in this region.

Animals↗

Serp2, an inhibitor of the interleukin-1beta-converting enzyme, is critical in the pathobiology of myxoma virus.

Recently, myxoma virus was shown to encode an additional member of the serpin superfamily. The viral gene, called serp2, was cloned, and the Serp2 protein was shown to specifically bind to interleukin-1beta (IL-1beta)-converting enzyme (ICE), thus inhibiting the cleavage of pro-IL-1beta by the protease (F. Petit, S. Bertagnoli, J. Gelfi, F. Fassy, C. Boucraut-Baralon, and A. Milon, J. Virol. 70:5860-5866, 1996). Here, we address the role of Serp2 in the development of myxomatosis, a lethal infectious disease of the European rabbit. A Serp2 mutant myxoma virus was constructed by disruption of the single-copy serp2 gene and insertion of the Escherichia coli gpt gene serving as the selectable marker. A revertant virus was obtained by replacing the E. coli gpt gene by the intact serp2 open reading frame. The Serp2(-) mutant virus replicated with wild-type kinetics both in rabbit fibroblasts and a rabbit CD4(+) T-cell line (RL5). Moderate reduction of cell surface levels of major histocompatibility complex I was observed after infection with wild-type or Serp2(-) mutant myxoma virus, and both produced white pocks on the chorioallantoic membrane of the chick embryo. After the infection of European rabbits, the Serp2(-) mutant virus proved to be highly attenuated compared to wild-type myxoma virus, as demonstrated by the clinical course of myxomatosis and the survival rates of infected animals. Pathohistological examinations revealed that infection with wild-type myxoma virus resulted in a blockade of the inflammatory response at the vascular level. In contrast, rapid inflammatory reactions occurred upon infection with the Serp2(-) mutant virus. Furthermore, lymphocytes in lymph nodes derived from animals inoculated with Serp2 mutant virus were shown to rapidly undergo apoptosis. We postulate that the virulence of myxoma virus in the European rabbit can be partially attributed to an impairment of host inflammatory processes and to the prevention of apoptosis in lymphocytes. The weakening of host defense is directly linked to serp2 gene function and is likely to involve the inhibition of IL-1beta-converting-enzyme-dependent pathways.

Animals↗

Monitoring the spread of myxoma virus in rabbit Oryctolagus cuniculus populations on the southern tablelands of New South Wales, Australia. II. Selection of a strain of virus for release.

To be able to study the dynamics of myxoma virus spread following a release in the field, a strain of virus is required that is both highly transmissible and readily differentiated from other field strains. Eight strains of virus of known virulence for laboratory rabbits and with previously mapped and sequenced restriction fragment length polymorphisms, were used to infect groups of seronegative wild rabbits. Based on these trials, and on the nature of the DNA polymorphism, a virus designated Brooklands/2-93 was chosen as a strain suitable for experimental release. These trials confirmed that resistance to myxomatosis within wild rabbit populations continues to be substantial and that some rabbits are highly resistant. These rabbits probably have little role in transmission of virus. Most of the virus strains tested induced very small or invisible primary lesions at the inoculation site. Thus the secondary skin sites such as eyelids, face and ears may be critical for transmission.

Animals↗

First field trial of a transmissible recombinant vaccine against myxomatosis and rabbit hemorrhagic disease.

As a novel approach for immunisation of wild rabbits, we have recently developed a transmissible vaccine against myxomatosis and rabbit hemorrhagic disease (RHD) based on a recombinant myxoma virus (MV) expressing the RHDV capsid protein [J. Virol. 74 (2000) 1114]. The efficacy and safety of the vaccine have been extensively evaluated under laboratory conditions. In this study, we report the first limited field trial of the candidate vaccine that was undertaken in an island of 34 Has containing a population of around 300 rabbits. Following administration by the subcutaneous route to 76 rabbits, the vaccine induced specific antibody responses against both myxomatosis and RHDV in all the inoculated rabbits. Furthermore, the recombinant virus exhibited a limited horizontal transmission capacity, promoting seroconversion of around 50% of the uninoculated rabbit population. No evidence of undesirable effects due to the recombinant virus field release was detected.

Animals↗

Monitoring the spread of myxoma virus in rabbit Oryctolagus cuniculus populations on the southern tablelands of New South Wales, Australia. III. Release, persistence and rate of spread of an identifiable strain of myxoma virus.

An identifiable strain of myxoma virus was introduced into four local populations of wild rabbits Oryctolagus cuniculus on the southern tablelands of New South Wales (NSW) and its spread in the presence of other field strains was monitored for 6 months. The main vector in this region was considered to be the European rabbit flea Spilopsyllis cuniculi. Each population of rabbits was of a high density and living in groups of warrens covering areas from 59 to 87 hectares. Rabbits occupying centrally located warrens were inoculated with the virus in late September or early October (spring) and the subsequent appearance of myxomatosis across the sites monitored by trapping, shooting and visual observations. Samples, taken from rabbits with myxomatosis, were examined by polymerase chain reaction (PCR) that allowed identification of the introduced strain. On all four sites the introduced virus spread from the inoculated rabbits in the centrally located warrens to rabbits in surrounding warrens. On Sites 1 and 3, this spread continued across the entire site persisting for at least 118 and 174 days respectively. On Sites 2 and 4, the virus was detected for 78 and 62 days respectively and the subsequent inability to detect the introduced virus correlated with the appearance of an unrelated field strain. Using three different methods of calculation, rates of spread ranged from 3.7 to 17.8 m d(-1).

Animals↗

Study of the virulence of five strains of amyxomatous myxoma virus in crossbred New Zealand White/Californian conventional rabbits, with evidence of long-term testicular infection in recovered animals.

The virulence of five amyxomatous myxoma virus (MV) strains, the clinical and pathogenetic effects of which had been studied previously in specific pathogen-free (SPF) rabbits, was determined by inoculation of five groups of 10 crossbred New Zealand White/Californian conventional rabbits. A much more acute myxomatosis syndrome was produced in conventional rabbits than that reproduced previously in SPF animals. However, the main clinical signs were of the respiratory type. The MV strains MYX 254/95 and 801 appeared very virulent, killing all the inoculated animals. The strains MYX 217/95, MYX 555/94 and Saint Benoist were somewhat attenuated, killing only seven, six and six rabbits, respectively. Extensive lung lesions due to supervening bacterial infections were observed in 36 of the 39 rabbits that died. Lethality was found to be a better estimate of virulence than mean survival time. By 98 days after viral inoculation, all the surviving animals had completely recovered. At that time, they were immunosuppressed by treatment with adrenocorticotrophic hormone (ACTH) for 10 days to determine whether they still harboured the virus. After the ACTH treatment, eight of the 11 surviving rabbits showed clinical signs that resembled amyxomatous myxomatosis. All the virological examinations performed on naso-conjunctival exudate, on mononuclear cells, on eyelids and on ovaries remained negative but infectious virus was isolated from the testes of three of six surviving male rabbits.

Adrenocorticotropic Hormone↗

Horizontal transmissible protection against myxomatosis and rabbit hemorrhagic disease by using a recombinant myxoma virus.

We have developed a new strategy for immunization of wild rabbit populations against myxomatosis and rabbit hemorrhagic disease (RHD) that uses recombinant viruses based on a naturally attenuated field strain of myxoma virus (MV). The recombinant viruses expressed the RHDV major capsid protein (VP60) including a linear epitope tag from the transmissible gastroenteritis virus (TGEV) nucleoprotein. Following inoculation, the recombinant viruses induced specific antibody responses against MV, RHDV, and the TGEV tag. Immunization of wild rabbits by the subcutaneous and oral routes conferred protection against virulent RHDV and MV challenges. The recombinant viruses showed a limited horizontal transmission capacity, either by direct contact or in a flea-mediated process, promoting immunization of contact uninoculated animals.

Animals↗

Patterns of parasite aggregation in the wild European rabbit (Oryctolagus cuniculus).

Understanding the factors controlling the distribution of parasites within their host population is fundamental to the wider understanding of parasite epidemiology and ecology. To explore changes in parasite aggregation, Taylor's power law was used to examine the distributions of five gut helminths of the wild rabbit. Aggregation was found to be a dynamic process that varied with year, season, host sex, age class, and myxomatosis. Yearly and seasonal changes are thought, in the main, to be the result of variations in weather conditions acting upon infectious stages (or intermediate hosts). Evidence in support of this was the comparatively low degree of fluctuation in the aggregation of the pinworm, Passalurus ambiguus, as the infectious stage of this parasite is likely to be less susceptible to environmental variation. Host age had a marked effect on the level of aggregation of all parasites, but this effect varied between parasite species. P. ambiguus, Trichostrongylus retortaeformis and Cittotaenia denticulata aggregation were lower in adult than juvenile rabbits whilst Graphidium strigosum and Mosgovoyia pectinata aggregation tended to increase with age. Host immunity is thought to be responsible for these differences. Differences in aggregation for different parasites were also seen when the rabbit population was split into males and females. Myxomatosis had a marked effect on helminth distribution with substantially less aggregation in rabbits showing clinical signs of the disease.

Age Factors↗

Interruption of cytokine networks by poxviruses: lessons from myxoma virus.

Myxoma virus is an infectious poxvirus pathogen that induces a virulent systemic disease called myxomatosis in European rabbits. The disease is rapidly and uniformly fatal to susceptible rabbits and is characterized by generalized dysfunction of cellular immunity and multiple interruptions of the host cytokine network. A number of virus genes are classified as virulence factors because virus constructs bearing targeted gene disruptions induce attenuated disease symptoms. Many of these genes encode proteins that interact directly with effector elements of the host immune system. Included among these immunosubversive viral proteins are secreted mimics of host ligands or regulators (virokines) and homologues of cellular cytokine receptors (viroceptors). Five examples of these immune modulator proteins encoded by myxoma virus are reviewed: (1) myxoma growth factor, a member of the epidermal growth factor ligand superfamily; (2) SERP-1, a secreted serine proteinase inhibitor; (3) M11L, a receptor-like surface protein; (4) T2, a tumor necrosis factor receptor homologue; and (5) T7, an interferon-gamma receptor homologue. The origin of viral strategies designed to subvert immune regulation by host cytokines is considered in the context of the biology of myxoma virus within immunocompetent hosts.

Animals↗

Enhancement of animal viruses growth on RK13 cells pretreated with 6-azauridine.

In these experiments a technique for enhancing the virus replication in tissue culture (RK13 cells) has been used. The method consisted in growing the cells in presence of mug 0.4-0.8 of 6-Azauridine/ml of cellular suspension until the monolayers were formed. This pretreatment enhances the replication of several animal viruses with increased infectious titers (vesicular stomatitis, equine arteritis, equine rhinopneumonitis, Aujeszky disease and myxomatosis virus) and with increased yield of total virus in the culture (myxomatosis virus). In other experiment the 6-Azauridine pretreatment of the cells has shown to render the cells more susceptible to interferon preparation action with subsequent high rate of vesicular stomatitis virus plaques reduction.

Animals↗

A review of mutual transmission of important infectious diseases between livestock and wildlife in Europe.

Oral vaccination of red foxes against rabies has been practiced in Europe since 1978 and has succeeded in greatly reducing the occurrence of this disease in foxes: this is an example of coordinated activity against a disease that affects both wild and domestic animals as well as humans. Some examples of diseases that affect both domestic and wild animals in Europe are: classical swine fever (hog cholera) in wild boars and domestic swine; myxomatosis and rabbit hemorrhagic disease in domestic and wild rabbits; bovine viral diarrhea (BVD) in cattle and roe deer; contagious ecthyma in domestic sheep and goats and also in, e.g., chamois, muskox, and reindeer; Mycobacterium bovis in cattle, wild boars, badgers, and deer; and brucellosis in a broad range of livestock and wildlife in all European countries. In addition, serological surveys performed in different free-ranging ungulate species revealed the presence of alphaherpesviruses related to bovine herpesvirus-1 in 7 European countries; and a study of malignant catarrhal fever in deer in Germany might indicate that in this case sheep are the main reservoir species. Although many data on infectious diseases are available in various European countries, there is more need for systematic surveillance and coordinated research.

Animals↗