Slow Virus Infection: Replication and Mechanisms of Persistence of Visna Virus in Sheep

Abstract

The influence of the age and immune status of the host on the slow replication and persistence of visna virus in sheep was studied. Twenty-five randomly bred fetal American lambs were inoculated intracerebrally with visna virus. Eight of these fetuses were immunosuppressed by thymectomy and antiserum to lymphocytes before inoculation. Fetuses were sacrificed sequentially, and tissues were processed for viral quantitation. No exponential increase of virus occurred in either the normal or immunosuppressed fetuses, and virus was recovered mainly by explanation of tissues. This finding indicated that the viral genome was present in tissue cells but that the extent of replication in the early phase of infection was restricted by factors unassociated with maturation or immune status of the host. In addition, virus isolated from the peripheral blood leukocytes of a sheep one year after inoculation was antigenically distinct from the plaque-purified virus used for inoculation. This distinction suggested that a major antigenic shift of the agent had occurred and provided another mechanism for the maintenance of the persistent infection.

Visna Virus-Induced Activation of MAPK Is Required for Virus Replication and Correlates with Virus-Induced Neuropathology

“…Sheep choroid plexus (SCP) cells and goat synovial membrane (GSM) cells were obtained as previously described (56)(57)(58) and cultured in minimum essential medium with Earle's salts (EMEM) (Life Technologies, Gaithersburg, Md.) supplemented with 50-g/ml gentamicin (Life Technologies) and 10% fetal bovine serum (FBS) (Atlanta Biologicals, Norcross, Ga.).…”

“…Visna virus causes interstitial pneumonitis, arthritis, mastitis, and inflammatory infiltration of the central nervous system (CNS) in sheep, months to years after initial infection, typifying the slow progressive onset of disease, hallmark of lentivirus infection (77,78,91). In vivo, the predominant target cells for visna virus infection are of the monocyte/macrophage lineage; however, virus replication is tightly regulated by both viral and cellular factors, such that infected monocytes do not express significant levels of viral mRNA or protein prior to maturation and differentiation into macrophages (32,33,58,77,78,91).…”

Ovine lentivirus-infected macrophages mediate productive infection in cell types that are not susceptible to infection with cell-free virus.

“…Typically, these viruses cause persistent infections and slowly progressive diseases that appear insidiously after incubation periods of more than 2 years in adult animals (Narayan et al, 1977 ;Sigurdsson, 1954). The ovine\caprine lentiviruses are strongly monocyte\macrophage-tropic and, to date, this is the main cell type shown to support productive virus replication in infected animals (Gendelman et al, 1985 ;Gorrell et al, 1992 ;Narayan et al, 1983).…”

Cerebrospinal fluid immunoglobulins in sheep with visna, a slow virus infection of the central nervous system☆

“…Visna is a chronic encephalomyelitis with occasional focal demyelinating lesions caused by a persistent infection by a naturally transmitted retrovirus of sheep (Gudnadottir 1974;Haase 1975;Narayan et al 1977;Petursson et al 1978;Nathanson et al 1980). We have underhaken a series of studies (Georgsson et al 1977(Georgsson et al , 1978Petursson et al 1976Petursson et al , 1978Petursson et al , 1980Nathanson et al 1979Nathanson et al ,, 1980 of the pathogenesis of visna following irtracerebral virus injection of Icelandic sheep, which are particularly susceptible to thi:, disease.…”