Retrovirus and comparative pathology
Retroviruses are RNAviruses that infect and can induce disease in humans and animals. Retroviral infections in small ruminants and horses share common features: when serology is available, infected animals can be seronegative; infected animals inconstantely develop disease; infection and disease can be experimentaly induced.
Animal retroviruses are a cause of spontaneous diseases, transmissible among animals and model systems of human diseases.
First of all…
Retroviruses are RNA viruses that infect and are likely to make humans and animals sick . The genus retrovirus includes takes seven families including alpharetroviruses (responsible especially leukemia in chickens), betaretro- viruses and lentiviruses.
Their small genome nevertheless allows to express structural genes, enzymatic activities ticks necessary for replication of the virus.
The the retroviral cycle is characterized by several stages health of infection with the production of retroviral particles. The two families responsible for illnesses in mammals are the lentiviruses, the main is HIV1 in humans, and betaretroviruses.
RETROVIRAL DISEASES IN SMALL RUMINANTS AND EQUIDAE
In the agronomic and veterinary field, these disease are expressed more particularly in small ruminants and equines. Small rumen lentiviruses nants represent a family of related retroviruses infecting either the goat (we speak then of virus caprine arthritis and encephalitis or CAEV), sheep (this is known as the Visna-Maedi or VMV virus). In France, more than a third of sheep and almost half of goats are infected with small rumen lentiviruses nants; there is a serological diagnosis.
The manifestos clinical conditions are arthritis, nerve damage (caprine encephalitis or Visna in sheep), a tire- Diffuse interstitial mopathy (Maedi in sheep). Finally breast involvement is constant and plays a role in the transmission of the virus including the main route is milk and colostrum. The infection lentiviral of the horse presents clinical manifestations distinct with recurrent episodes of fever and thrombopenia, the virus is vector-borne (tabanidae).
Like the lentivi- rus of small ruminants and IVF in cats, the equine infectious anemia virus has remained responsible for interstitial lung disease. In total, lentiviruses are responsible for similar lesions of a species to another.
The only particularity is the presence of an immune deficiency in primates infected with SIV or HIV, in infected cats by IVF. Sheep adenocarcinoma is a lung cancer transmissible associated with infection by the exogenous form of a beta-retrovirus (Jaagsiekte sheep retrovirus, JSRV). It manifests clinically by abundant discharge of mucoid secretions from nasal passages. There is currently no clinical diagnosis.
Like many retroviruses, there is a counterpart endogenous (endogenous sheep retrovirus or ESRV). Its consequences are not well known, but this disease seems endemic in certain French regions. Infections retrovirals of small ruminants and equines have common features: when there is a diagnosis serologically, infected animals can be seronegative; infected animals are not always sick; infection and disease can be reproduced experimentally.
INTERSPECIFIC PASSAGE OF LENTIVIRUSES
Lentiviruses are capable of interspecific passages. This has been shown between sheep and goats. Especially the main interspecific passage as far as man was the estate of seven passages between 1914 and 1941 of the chimpanzee and the green African monkey SIV leading to the respective establishment- HIV1 and HIV2 infections. The transition from small domestic ruminants to CAEV wild is possible naturally and experimentally, then leading to the establishment of a clinically different infection. However, the passage of CAEV in humans seems impossible due to lack of ability to affect human cells.
Of even infectivity with this swine cell virus is inconsistent, while the infectivity of bovine cells is possible and especially that in vivo infection of cattle can be established nevertheless leading to an abortive infection. As with all retroviruses, crossing the species barrier is easy when species are close and generally difficult when species are distant.
ROLE OF REGULATORY GENES AND ACCESSORIES LENTIVIRUSES
The lentivirus genome is characterized by the presence additional reading frames compared to retro- simple viruses. The function of the products of these genes is often poorly known. This is how the tat gene of CAEV was appointed because of its genetic organization; in fact the product of this gene does not have a tat-like function like primate lentiviruses, that is, it has no effect on the level of replication of the virus; it especially induces the arrest of cells in phase G2 of the cell cycle, classically recognized function for the primate lentiviruses vpr genes.
Similarly, the role of several of the regulated genes primate lentivirus readers or accessories is poorly known. It is generally studied in vitro under conditions necessarily artificial. It can only rarely be studied in vivo, in particular in monkeys. Most of study systems simultaneously analyze infection of macrophages and lymphocytes, since HIV and SIV infect these two cell populations. In contrast, the small ruminant lentiviruses do not infect lymphocytes and infect only monocytes and macrophages. CAEV-based genetic constructs can express the regulatory or accessory genes of lentivirus of primates. These are viruses that infect only macrophages and monocytes, to study the indirect effects on lymphocyte populations . Small ruminant lentiviruses are then becomes an important tool for studying the mechanisms of HIV infection.
THE SHEEP PULMONARY ADENOCARCINOMA IS ASSOCIATED TO A RETROVIRUS
Ovine pulmonary adenocarcinoma is a transmissible associated with the JSRV (Jaagsiekte Sheep) retrovirus Retrovirus). A form related to this retrovirus exists from endogenously in the genome of sheep and goats. A potential carcinogenesis mechanism could be linked when the exogenous form is inserted into the normal genome retroviral.
To determine the integration sites, he first determined the location of the endogenous form from JSRV (ESRV). The normal sheep genome has one twenty copies. The virus JSRV is constantly associated with lesions of ovine lung adenocarcinoma. To date there is no diagnostic infection with this virus.
JSRV MAY HAVE A NEW ONCOGEN
The usual carcinogenesis mechanisms (activation oncogenes, inactivation of anti-oncogenes) are not implemented during pulmonary adenocarcinoma sheep; similarly, there is a low replication rate of cancer cells which are mainly pneumo-type 2 cytes.
Next to the insertional mutagenesis already mentioned, the carcinogenesis could be due to the product of a gene to unknown function called X from JSRV. This gene kept in within JSRV isolates is expressed, its structure and function are being characterized.
WHY BE INTERESTED TO ANIMALS RETROVIRUS ?
Animal retroviruses induce, when they sick animals, clinical symptoms (arthritis, pneumonia, anemia). Sick animals are culled, infected animals and their products (sperm, oocytes, etc.) are above export limitation receipts when they come from from seropositive animals. These different observations have led to the implementation in France of two control or eradication of CAEV first, then of VMV. Their effectiveness is currently the subject of controversy. He there is an industrial demand in the field of assisted reproduction and diagnosis (for EIAV and JSRV).
The societal demand is clear with regard to the quality of the milk and the interspecific passage. In this context, scientific watch is an obligation because from the perspective of using lentiviral vectors and xenograft. Finally, the breeders are seeking advice in the area of the breeding line either for the breeding line or for herd reconstruction in the event of eradication VMV and CAEV, i.e. for the conduct to be taken vis-à-vis the wildlife. This set of observations led as part of the COST action to organize a conference of consensus in the fall of 2002 on the control of lentiviral infections of small ruminants .
Finally, retroviral diseases animals are good models of human pathology. Arthritis in CAEV-infected goats is close to rheumatoid arthritis, pneumonia interstitial of VMV infected sheep is close to Diffuse interstitial lung disease in humans and especially ovine pulmonary adenocarcinoma is similar to a human disease called bronchiolo-alveolar cancer. Spontaneously fect mononuclear phagocytes without infect lymphocytes during CAEV infection allows to study specifically the role of certain genes accessories of primate lentiviruses (SIV and HIV). At total animal retroviruses especially small ruminant and equines are a cause of spontaneous born, transmissible in these animals and a model of more human diseases.