scholarly journals The vif gene of maedi-visna virus is essential for infectivity in vivo and in vitro

Virology ◽  
2004 ◽  
Vol 318 (1) ◽  
pp. 350-359 ◽  
Author(s):  
Helga Bryndı́s Kristbjörnsdóttir ◽  
Valgerdur Andrésdóttir ◽  
Vilhjálmur Svansson ◽  
Sigurbjörg Torsteinsdóttir ◽  
Sigrı́dur Matthı́asdóttir ◽  
...  
Keyword(s):  
Visna Virus ◽  
Maedi Visna Virus

scholarly journals Maedi-visna virus Vif protein uses motifs distinct from HIV-1 Vif to bind zinc and cofactor required for A3 degradation

2020 ◽  
pp. jbc.RA120.015828
Author(s):  
Kirsten M. Knecht ◽  
Yingxia Hu ◽  
Diana Rubene ◽  
Matthew Cook ◽  
Samantha J Ziegler ◽  
...  
Keyword(s):  
Viral Infections ◽  
Zinc Ion ◽  
Binding Motif ◽  
Cytidine Deaminases ◽  
Visna Virus ◽  
Primate Lentiviruses ◽  
Maedi Visna Virus ◽  
Hiv 1

The mammalian apolipoprotein B mRNA-editing enzyme catalytic polypeptide-like 3 (APOBEC3 or A3) family of cytidine deaminases restrict viral infections by mutating viral DNA and impeding reverse transcription. To overcome this antiviral activity, most lentiviruses express a viral accessory protein called Vif, which recruits A3 proteins to Cullin-RING E3 ubiquitin ligases such as Cul5 for ubiquitylation and subsequent proteasomal degradation. While Vif proteins from primate lentiviruses like HIV-1 utilize the transcription factor CBFβ as a non-canonical cofactor to stabilize the complex, maedi-visna virus (MVV) Vif hijacks cyclophilin A (CypA) instead. Since CBFβ and CypA are both highly conserved among mammals, the requirement for two different cellular cofactors suggests that these two A3-targeting Vif proteins have different biochemical and structural properties. To investigate this topic, we used a combination of in vitro biochemical assays and in vivo A3 degradation assays to study motifs required for MVV Vif to bind zinc ion, Cul5, and the cofactor CypA. Our results demonstrate that while some common motifs between HIV-1 Vif and MVV Vif are involved in recruiting Cul5, different determinants in MVV Vif are required for cofactor binding and stabilization of the E3 ligase complex, such as the zinc-binding motif and N- and C-terminal regions of the protein. Results from this study advance our understanding of the mechanism of MVV Vif recruitment of cellular factors and the evolution of lentiviral Vif proteins.

scholarly journals Implication of caspases during maedi–visna virus-induced apoptosis

2002 ◽  
Vol 83 (12) ◽  
pp. 3153-3161 ◽  
Author(s):  
R. Duval ◽  
V. Bellet ◽  
S. Delebassée ◽  
C. Bosgiraud
Keyword(s):  
Cell Death ◽  
Caspase 3 ◽  
Specific Cell ◽  
Caspase 9 ◽  
Virus Growth ◽  
Caspase Inhibitors ◽  
Visna Virus ◽  
Maedi Visna Virus ◽  
Cellular Lysis

Maedi–visna virus (MVV) causes encephalitis, pneumonia and arthritis in sheep. In vitro, MVV infection and replication lead to strong cytopathic effects characterized by syncytia formation and subsequent cellular lysis. It was demonstrated previously that MVV infection in vitro induces cell death of sheep choroid plexus cells (SCPC) by a mechanism that can be associated with apoptotic cell death. Here, the relative implication of several caspases during acute infection with MVV is investigated by employing diverse in vitro and in situ strategies. It was demonstrated using specific pairs of caspase substrates and inhibitors that, during in vitro infection of SCPC by MVV, the two major pathways of caspase activation (i.e. intrinsic and extrinsic pathways) were stimulated: significant caspase-9 and -8 activities, as well as caspase-3 activity, were detected. To study the role of caspases during MVV infection in vitro, specific, cell-permeable, caspase inhibitors were used. First, these results showed that both z-DEVD-FMK (a potent inhibitor of caspase-3-like activities) and z-VAD-FMK (a broad spectrum caspase inhibitor) inhibit caspase-9, -8 and -3 activities. Second, both irreversible caspase inhibitors, z-DEVD-FMK and z-VAD-FMK, delayed MVV-induced cellular lysis as well as virus growth. Third, during SCPC in vitro infection by MVV, cells were positively stained with FITC-VAD-FMK, a probe that specifically stains cells containing active caspases. In conclusion, these data suggest that MVV infection in vitro induces SCPC cell death by a mechanism that is strongly dependent on active caspases.

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

2005 ◽  
Vol 79 (24) ◽  
pp. 15038-15042 ◽  
Author(s):  
Bjarki Gudmundsson ◽  
Stefán Ragnar Jónsson ◽  
Oddur Ólafsson ◽  
Gudrún Agnarsdóttir ◽  
Sigrídur Matthíasdóttir ◽  
...  
Keyword(s):  
Defense Mechanisms ◽  
Differential Growth ◽  
Nucleotide Substitutions ◽  
Highly Pathogenic ◽  
Visna Virus ◽  
Primate Lentiviruses ◽  
The Central Nervous System ◽  
Growth Phenotype ◽  
Maedi Visna Virus

ABSTRACT Maedi-visna virus (MVV) is a lentivirus of sheep sharing several key features with the primate lentiviruses. The virus causes slowly progressive diseases, mainly in the lungs and the central nervous system of sheep. Here, we investigate the molecular basis for the differential growth phenotypes of two MVV isolates. One of the isolates, KV1772, replicates well in a number of cell lines and is highly pathogenic in sheep. The second isolate, KS1, no longer grows on macrophages or causes disease. The two virus isolates differ by 129 nucleotide substitutions and two deletions of 3 and 15 nucleotides in the env gene. To determine the molecular nature of the lesions responsible for the restrictive growth phenotype, chimeric viruses were constructed and used to map the phenotype. An L120R mutation in the CA domain, together with a P205S mutation in Vif (but neither alone), could fully convert KV1772 to the restrictive growth phenotype. These results suggest a functional interaction between CA and Vif in MVV replication, a property that may relate to the innate antiretroviral defense mechanisms in sheep.

scholarly journals Targeting of the Visna Virus Tat Protein to AP-1 Sites: Interactions with the bZIP Domains of Fos and Jun In Vitro and In Vivo

1999 ◽  
Vol 73 (1) ◽  
pp. 37-45 ◽  
Author(s):  
B. A. Morse ◽  
L. M. Carruth ◽  
J. E. Clements
Keyword(s):  
Transcription Factors ◽  
Protein Interactions ◽  
Tat Protein ◽  
Protein Protein Interactions ◽  
Viral Promoter ◽  
Visna Virus ◽  
Cellular Transcription ◽  
Virus Promoter

ABSTRACT The visna virus Tat protein is required for efficient viral transcription from the visna virus long terminal repeat (LTR). AP-1 sites within the visna virus LTR, which can be bound by the cellular transcription factors Fos and Jun, are also necessary for Tat-mediated transcriptional activation. A potential mechanism by which the visna virus Tat protein could target the viral promoter is by protein-protein interactions with Fos and/or Jun bound to AP-1 sites in the visna virus LTR. Once targeted to the visna virus promoter, the Tat protein could then interact with basal transcription factors to activate transcription. To examine protein-protein interactions with cellular proteins at the visna virus promoter, we used an in vitro protein affinity chromatography assay and electrophoretic mobility shift assay, in addition to an in vivo two-hybrid assay, to show that the visna virus Tat protein specifically interacts with the cellular transcription factors Fos and Jun and the basal transcription factor TBP (TATA binding protein). The Tat domain responsible for interactions with Fos and Jun was localized to an alpha-helical domain within amino acids 34 to 69 of the protein. The TBP binding domain was localized to amino acids 1 to 38 of Tat, a region previously described by our laboratory as the visna virus Tat activation domain. The bZIP domains of Fos and Jun were found to be important for the interactions with Tat. Mutations within the basic domains of Fos and Jun abrogated binding to Tat in the in vitro assays. The visna virus Tat protein was also able to interact with covalently cross-linked Fos and Jun dimers. Thus, the visna virus Tat protein appears to target AP-1 sites in the viral promoter in a mechanism similar to the interaction of human T-cell leukemia virus type 1 Tax with the cellular transcription factor CREB, by binding the basic domains of an intact bZIP dimer. The association between Tat, Fos, and Jun would position Tat proximal to the viral TATA box, where the visna virus Tat activation domain could contact TBP to activate viral transcription.

Maedi-visna virus, a model for in vitro testing of potential anti-HIV drugs

2001 ◽  
Vol 24 (2) ◽  
pp. 113-122 ◽  
Author(s):  
D Salvatori ◽  
S Vincenzetti ◽  
G Maury ◽  
G Gosselin ◽  
G Gaubert ◽  
...  
Keyword(s):  
In Vitro Testing ◽  
Visna Virus ◽  
Maedi Visna Virus ◽  
Hiv Drugs ◽  
Anti Hiv

Effect of in vitro maedi-visna virus infection on adherence and phagocytosis of staphylococci by ovine cells

1997 ◽  
Vol 57 (1) ◽  
pp. 13-28 ◽  
Author(s):  
E. Monleón ◽  
M.C. Pacheco ◽  
L. Luján ◽  
R. Bolea ◽  
D.F. Luco ◽  
...  
Keyword(s):  
Virus Infection ◽  
Visna Virus ◽  
Maedi Visna Virus

In vivo depletion of CD8+ cells does not affect primary maedi visna virus infection in sheep

1999 ◽  
Vol 70 (3-4) ◽  
pp. 173-187 ◽  
Author(s):  
Kristina Eriksson ◽  
Elizabeth McInnes ◽  
Susanna Ryan ◽  
Paul Tonks ◽  
Ian McConnell ◽  
...  
Keyword(s):  
Virus Infection ◽  
Cd8 Cells ◽  
Visna Virus ◽  
Maedi Visna Virus

scholarly journals Infection of Dendritic Cells by the Maedi-Visna Lentivirus

2000 ◽  
Vol 74 (21) ◽  
pp. 10096-10103 ◽  
Author(s):  
Susanna Ryan ◽  
Laurence Tiley ◽  
Ian McConnell ◽  
Barbara Blacklaws
Keyword(s):  
T Cells ◽  
Dendritic Cells ◽  
Cell Types ◽  
Infected Sheep ◽  
In Vivo Model ◽  
Visna Virus ◽  
Afferent Lymph ◽  
Infection Experiments

ABSTRACT The early stages of lentivirus infection of dendritic cells have been studied in an in vivo model. Maedi-visna virus (MVV) is a natural pathogen of sheep with a tropism for macrophages, but the infection of dendritic cells has not been proven, largely because of the difficulties of definitively distinguishing the two cell types. Afferent lymphatic dendritic cells from sheep have been phenotypically characterized and separated from macrophages. Dendritic cells purified from experimentally infected sheep have been demonstrated not only to carry infectious MVV but also to be hosts of the virus themselves. The results of the in vivo infection experiments are supported by infections of purified afferent lymph dendritic cells in vitro, in which late reverse transcriptase products are demonstrated by PCR. The significance of the infection of afferent lymph dendritic cells is discussed in relation to the initial spread of lentivirus infection and the requirement for CD4 T cells.

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