Bovine leukemia virus inhibition in vitro by ribavirin

ABSTRACT The cytoplasmic domain of an envelope transmembrane glycoprotein (gp30) of bovine leukemia virus (BLV) has two overlapping copies of the (YXXL)2 motif. The N-terminal motif has been implicated in in vitro signal transduction pathways from the external to the intracellular compartment and is also involved in infection and maintenance of high viral loads in sheep that have been experimentally infected with BLV. To determine the role of YXXL sequences in the replication of BLV in vitro, we changed the tyrosine or leucine residues of the N-terminal motif in an infectious molecular clone of BLV, pBLV-IF, to alanine to produce mutated proviruses designated Y487A, L490A, Y498A, L501A, and Y487/498A. Transient transfection of African green monkey kidney COS-1 cells with proviral DNAs that encoded wild-type and mutant sequences revealed that all of the mutated proviral DNAs synthesized mature envelope proteins and released virus particles into the growth medium. However, serial passages of fetal lamb kidney (FLK) cells, which are sensitive to infection with BLV, after transient transfection revealed that mutation of a second tyrosine residue in the N-terminal motif completely prevented the propagation of the virus. Similarly, Y498A and Y487/498A mutant BLV that was produced by the stably transfected COS-1 cells exhibited significantly reduced levels of cell-free virion-mediated transmission. Analysis of the protein compositions of mutant viruses demonstrated that lower levels of envelope protein were incorporated by two of the mutant virions than by wild-type and other mutant virions. Furthermore, a mutation of a second tyrosine residue decreased the specific binding of BLV particles to FLK cells and the capacity for viral penetration. Our data indicate that the YXXL sequences play critical roles in both viral entry and the incorporation of viral envelope protein into the virion during the life cycle of BLV.

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El componente racial influencia la resistencia a la infección con el virus de la leucosis bovina

Revista de la Facultad de Medicina Veterinaria y de Zootecnia ◽

10.15446/rfmvz.v65n2.75632 ◽

2018 ◽

Vol 65 (2) ◽

Author(s):

Cristina Úsuga-Monroy ◽

José Julian Echeverri ◽

Albeiro López-Herrera

Keyword(s):

Infection Rate ◽

Vesicular Stomatitis Virus ◽

Bovine Leukemia Virus ◽

Leukemia Virus ◽

Foot And Mouth Disease ◽

Holstein Breed ◽

Mouth Disease Virus ◽

Significant Difference ◽

Vesicular Stomatitis

The bovine leukemia virus (BLV) is a retrovirus that primarily affects dairy cattle, reducing milk production between 2.5 and 5%. The Colombian Blanco Orejinegro (BON) is a well-adapted, rustic, creole breed resistant to in vitro infections of Foot-and-mouth disease virus and vesicular stomatitis virus, as well as to Brucella abortus. This study aimed to determine if the crossing of BON and Holstein breeds is resistant to infection by BLV. Blood samples of 124 individuals (59 Holstein, 40 BON, and 25 BON x HOL) of the same herd were taken. The DNA was extracted, and a nested PCR was performed related to a region of the env gene of BLV. A fragment of 444 bp was obtained for positives animals. The molecular in-herd prevalence was 33% for BLV. A significant difference for BLV infection was found among the groups (p<0.05). The infection rate for the Holstein group was 55.9%, for BON cattle 5%, and for BON x HOL cattle 24%. The latter showed a reduction in the infection rate of 32% to the Holstein breed, which can be attributed to the presence of resistance genes in the BON breed. It was found that the level of infection is lower in BON x HOL cattle in contrast with Holstein dairy cows.

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Early polykaryocytosis inhibition: A simple quantitative in vitro assay for the detection of bovine leukemia virus infection in cattle

European Journal of Cancer (1965) ◽

10.1016/0014-2964(78)90097-x ◽

1978 ◽

Vol 14 (8) ◽

pp. 811-827 ◽

Cited By ~ 7

Author(s):

B. Guillemain ◽

R. Mamoun ◽

D. Levy ◽

T. Astier ◽

K. Irgens ◽

...

Keyword(s):

Virus Infection ◽

Bovine Leukemia Virus ◽

Leukemia Virus ◽

In Vitro Assay ◽

Bovine Leukemia Virus Infection ◽

Vitro Assay

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Effect of bovine leukemia virus infection on bovine peripheral blood monocyte responsiveness to lipopolysaccharide stimulation in vitro

Veterinary Immunology and Immunopathology ◽

10.1016/0165-2427(95)05419-7 ◽

1995 ◽

Vol 48 (1-2) ◽

pp. 77-88 ◽

Cited By ~ 11

Author(s):

D. Werling ◽

M. Sileghem ◽

H. Lutz ◽

W. Langhans

Keyword(s):

Virus Infection ◽

Peripheral Blood ◽

Bovine Leukemia Virus ◽

Leukemia Virus ◽

Peripheral Blood Monocyte ◽

Blood Monocyte ◽

Bovine Leukemia Virus Infection

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PRMT5 Is Required for Bovine Leukemia Virus Infection In Vivo and Regulates BLV Gene Expression, Syncytium Formation, and Glycosylation In Vitro

Viruses ◽

10.3390/v12060650 ◽

2020 ◽

Vol 12 (6) ◽

pp. 650 ◽

Cited By ~ 1

Author(s):

Wlaa Assi ◽

Tomoya Hirose ◽

Satoshi Wada ◽

Ryosuke Matsuura ◽

Shin-nosuke Takeshima ◽

...

Keyword(s):

Gene Expression ◽

Small Molecule ◽

Bovine Leukemia Virus ◽

Proviral Load ◽

Leukemia Virus ◽

Syncytium Formation ◽

High Proviral Load

Bovine leukemia virus (BLV) is the causative agent of enzootic bovine leukosis, which is the most common neoplastic disease of cattle and is closely related to human T-cell leukemia viruses. We investigated the role of a new host protein, PRMT5, in BLV infection. We found that PRMT5 is overexpressed only in BLV-infected cattle with a high proviral load, but not in those with a low proviral load. Furthermore, this upregulation continued to the lymphoma stage. PRMT5 expression was upregulated in response to experimental BLV infection; moreover, PRMT5 upregulation began in an early stage of BLV infection rather than after a long period of proviral latency. Second, siRNA-mediated PRMT5 knockdown enhanced BLV gene expression at the transcript and protein levels. Additionally, a selective small-molecule inhibitor of PRMT5 (CMP5) enhanced BLV gene expression. Interestingly, CMP5 treatment, but not siRNA knockdown, altered the gp51 glycosylation pattern and increased the molecular weight of gp51, thereby decreasing BLV-induced syncytium formation. This was supported by the observation that CMP5 treatment enhanced the formation of the complex type of N-glycan more than the high mannose type. In conclusion, PRMT5 overexpression is related to the development of BLV infection with a high proviral load and lymphoma stage and PRMT5 inhibition enhances BLV gene expression. This is the first study to investigate the role of PRMT5 in BLV infection in vivo and in vitro and to reveal a novel function for a small-molecule compound in BLV-gp51 glycosylation processing.

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