Mutational analysis of a principal neutralization domain of visna/maedi virus envelope glycoprotein.

We have shown previously that a type-specific neutralization domain is located within a 39 aa sequence in the fourth variable domain of gp135 in visna/maedi virus. We now show that neutralizing antibodies detected early in infection are directed to this epitope, suggesting an immunodominant nature of this domain. Ten antigenic variants were previously analysed for mutations in this region, and all but one were found to be mutated. To assess the importance of these mutations in replication and neutralization, we reconstructed several of the mutations in an infectious molecular clone and tested the resulting viruses for neutralization phenotype and replication. Mutation of a conserved cysteine was shown to alter the neutralization epitope, whilst the replication kinetics in macrophages were unchanged. Mutations modulating potential glycosylation sites were found in seven of the ten antigenic variants. A frequently occurring mutation, removing a potential glycosylation site, had no effect on its own on the neutralization phenotype of the virus. However, adding an extra potential glycosylation site in the region resulted in antigenic escape. The results indicate that the conserved cysteine plays a role in the structure of the epitope and that glycosylation may shield the principal neutralization site.

Vaccination of sheep with Maedi-visna virus gag gene and protein, beneficial or harmful?

In spite of intense efforts no vaccine is yet available that protects against lentiviral infections. Sheep were immunised eight times over a period of 2.5 years with the maedi-visna (MVV) gag gene on two different vectors, 2 sheep with VR1012-gag-CTE and 2 sheep with pcDNA3.1-gag-CTE. All sheep responded to some of the mature MVV Gag proteins in Western blot (WB). Three of them responded to the virus in lymphocyte proliferation test. The sheep received a boost with recombinant Gag protein resulting in elevated antibody response. However, when they were challenged intratracheally with MVV they all became immediately infected as judged by a strong rise in antibody titer and virus isolation from blood. It is therefore clear that the vaccination gave no protection. It is even possible that it facilitated infectivity since virus was isolated earlier from all the vaccinated sheep than from any of the unvaccinated sheep infected in the same way with the same dose.

Immune response to maedi-visna virus.

The ovine maedi-visna virus (MVV) was the first lentivirus to be isolated and characterized 1957 in Iceland. MVV leads to a life-long, persistent infection with slow development of lesions in the lung and the central nervous system (CNS). The main target cells of MVV are of the monocyte/macrophage lineage and it does not infect T-lymphocytes or cause immune suppression like human immune deficiency virus (HIV). In spite of a fairly good immune response, including both neutralizing antibodies and cytotoxic T lymphocytes, the virus persists in the host and establishes a life-long infection. There are strong indications that the pathological lesions are immune-mediated and vaccination attempts have not only failed to induce sterile immunity but have occasionally caused increased viremia and more severe disease.

Mucosal vaccination with an attenuated maedi-visna virus clone.

Four sheep were infected intratracheally with an attenuated molecular clone of maedi-visna virus (MVV). All four became infected. Ten months later these sheep were challenged intratracheally with a genetically similar but pathogenic clone of MVV. Four unvaccinated sheep were infected simultaneously. All sheep became infected by the challenge virus. The vaccinated sheep were not protected against superinfection with the challenge clone. However, virus was isolated more frequently from the blood of the unvaccinated controls than of the vaccinated animals and ten times more frequently from lungs of unvaccinated sheep than from lungs of vaccinated sheep at sacrifice, indicating partial protection.

Routes of transmission and consequences of small ruminant lentiviruses (SRLVs) infection and eradication schemes.

Small ruminant lentiviruses (SRLV = maedi-visna in sheep and caprine arthritis encephalitis in goats) are distributed throughout most countries of the world, particularly Europe. Laboratories from 16 European countries established collaborations within the framework of a COST (CO-operation in the field of Scientific and Technical Research) action sponsored by the European Union in order to (i) better organize their research programmes on SRLVs and (ii) to coordinate efforts to combat these two diseases. After five years, a consensus conference--the first one in the veterinary medicine field--concluded the work of this network of laboratories by reviewing the present position and discussing three important questions in the field of SRLVs: routes of transmission, consequences of infection and potential role of eradication programmes at either a European or local level, according to the situation in each country or region. This paper brings together existing information regarding these questions and identifies areas for future research.