Characterization of a New York ovine lentivirus isolate.

A lentivirus has been isolated from a Finnish ewe with ovine progressive pneumonia in a closed upstate New York flock. We demonstrated that the virus, designated ovine lentivirus strain CU1 (OLV-CU1), is biologically, biochemically and molecularly related to, but distinct from, previously described sheep and goat lentiviruses. Nine of 32 ewes (from the affected flock) with precipitating antibodies for ovine lentivirus also produced antibodies that were able to neutralize the infectivity of OLV-CU1. The virus replicated in cultured sheep fibroblasts and caused the formation of large multi-nucleated cells. OLV-CU1-specific RNA transcripts found in infected cells and virion antigenic proteins were similar to those of other small ruminant lentiviruses. However, the virus was distinguished from other isolates at the DNA level by nucleic acid hybridization, restriction endonuclease mapping and partial sequencing of the virus genome.

Identification and subcellular localization of the Q gene product of visna virus.

The genome of the sheep visna lentivirus contains an open reading frame, Q, which has a coding potential of 230 amino acid residues. This paper reports the identification and the subcellular localization of the Q ORF-encoded protein detected in lysates of visna virus-infected sheep choroid plexus cells. Sera from sheep either experimentally or naturally infected with visna virus reacted with the bacterially synthesized Q protein indicating that the in vivo expressed Q product is immunogenic. Antibodies raised against a synthetic N-terminal peptide, reacted with either the bacterial Q or the in vitro translated Q protein as well as with the Q protein expressed during cellular infection. This 29 kDa protein is detectable late in the lytic viral cycle, i.e., 72 hr postinfection, and this expression correlates with the late transcription of its 4.8-kb mRNA. These results provide evidence for the first time that the Q ORF is a late gene of visna virus and that the Q protein is located in the cytosol compartment, without evidence of accumulation at the cell membrane, or in cell-free virion particles.

Molecular studies of viral pathogenesis in the central nervous system. The Linacre Lecture 1991.

What is the molecular biological basis of viral pathogenesis in the central nervous system (CNS), ie by what molecular mechanisms do different viruses produce particular patterns of neurological disease in man and animal models, and can one use molecular techniques to ascertain the viral aetiology of certain neurological conditions? This complex subject can be approached in three different but interrelated ways. First, one may relate molecular techniques to specific biological properties such as viral spread to the CNS, to neurotropism, ie the affinity of the virus for particular neural regions and cells, and to neurovirulence, which refers to the actual ability to cause neurological disease. Second, the reverse approach can be adopted by considering these different aspects of virus-host relationships and then how the techniques have contributed to their understanding. Third, one can select specific neurotropic viruses, such as polio or herpes viruses, and then relate these to both particular techniques and pathogenetic mechanisms [1]. The second component of this paper will deal with the immunopathological mechanisms seen in three specific CNS viral infections, all of which have been the focus of study in the author's laboratory over the past six years.

Human and ovine lentiviral infections compared.

Maedi-visna virus (MVV) of sheep was the first lentivirus to be isolated. The genomic organization of MVV is very similar to that of human immunodeficiency virus (HIV) with several genes regulating the expression of the viral genome. Viral replication is severely restricted in the host and some cells apparently contain the genetic information in a DNA provirus form with little or no expression of viral antigens. This seems to be a major factor in causing the "slowness" of lentiviral infections and the persistence of the virus in the host since the immune system may not recognize the provirus-containing cells. The target cells for HIV and MVV are similar although T4 lymphocytes are not specifically destroyed in maedi-visna. There are also certain similarities in the pathological changes in both diseases, both in the central nervous system, the lungs and the lymphatic system. Although the severe final immunodeficiency state characteristic of AIDS has not been observed in maedi-visna, the basic biological features of the MVV and its interaction with host cells are so similar to HIV infection, that we consider ovine maedi-visna useful animal model for the human lentivirus infections.