In Vivoandin VitroInfection with Two Different Molecular Clones of Visna Virus

Abstract

The behavior of two genetically different molecular clones of visna virus KV1772-kv72/67 and LV1-1KS1 was compared in vivo and in vitro. On intracerebral inoculation, clone KV1772-kv72/67 induced a similar response in five sheep as has already been reported with neurovirulent derivates of visna virus. Virus was frequently isolated from blood, cerebrospinal fluid (CSF), and lymphoid organs and induced characteristic central nervous system (CNS) lesions. A strong humoral immune response was detected by ELISA, immunoblotting, and neutralization. Six sheep infected with clone LV1-1KS1 showed a completely different picture. No virus could be isolated from blood or CSF during 6 months of infection. At sacrifice all organs were virus-negative except the CNS of one sheep. None of the six sheep developed significant neutralizing antibodies and only low titer antibodies were detected by ELISA and immunoblotting. Minimal CNS lesions were present in one sheep. The molecular clones were also tested in sheep choroid plexus cells (SCP) and macrophages. In macrophages LV1-1KS1 replicated to a significantly lower titer but induced much more cell fusion than KV1772-kv72/67. The clones replicated equally well in SCP cells. Thus, these molecular clones of visna virus, which differ only by 1% in nucleotide sequence, showed a profound difference in replication and pathogenicity both in vitro and in vivo. These results can be used to map viral genetic determinants important for host-lentivirus interactions.

Simultaneous Mutations in CA and Vif of Maedi-Visna Virus Cause Attenuated Replication in Macrophages and Reduced Infectivity In Vivo

“…Virus was isolated from the buffy coat as described previously (33). The following organs were tested for presence of infectious virus by coculture with SCP cells (24) on May 8, 2018 by guest http://jvi.asm.org/ cerebellum, spleen, cervical, mediastinal and mesenteric lymph nodes, bone marrow, and lungs (one sample from each lobe).…”

“…The KS1 strain has repeatedly been shown to be nonpathogenic in sheep, whereas the KV1772 strain is highly pathogenic (33). Of 219 attempts to isolate virus from blood of sheep infected with KS1 in various experiments, virus was isolated only on one occasion.…”

“…In this study, we examined the different cell tropism and pathogenicity of two molecular clones of MVV (2,33). One of the clones (KS1) replicates well in SCP cells, but replicates only to low titers in macrophages, and is nonpathogenic in sheep.…”

Immunization against Small Ruminant Lentiviruses

“…Icelandic researchers explored, subsequently, the use of a low pathogenic molecular clone, which differed only by 1% in nucleotide sequence from a highly pathogenic molecular clone, both obtained from Icelandic infected sheep using molecular biology engineering [35]. Intratracheal inoculation with high doses (10 7 TCID 50 ) of the low pathogenic clone induced low antibody titers, suggesting a Th1-biased response.…”

Envelope Gene-Mediated Neurovirulence in Feline Immunodeficiency Virus Infection: Induction of Matrix Metalloproteinases and Neuronal Injury

“…For example, small amino acid changes in the surface unit (SU) or transmembrane (TM) glycoprotein of FIV determine cell tropism (30,36,(52)(53)(54), receptor profiles (59), and cytopathogenicity (30,36). Similar regions within the envelope gene have also been shown to influence the development of neurological disease in various retroviral systems, conferring a neurovirulent phenotype on otherwise nonneurovirulent viral strains (27,31,42,49). Although the basis for these phenotypic differences is unclear, several studies have implicated the ability of these regions to influence cell tropism (4,9,48,52) and the release of toxic molecules by infected cells (14,26,29,43).…”