scholarly journals CAT1/SLC7A1 acts as a cellular receptor for bovine leukemia virus infection

2019 ◽  
Author(s):  
Lanlan Bai ◽  
Hirotaka Sato ◽  
Yoshinao Kubo ◽  
Satoshi Wada ◽  
Yoko Aida
Keyword(s):  
Cell Surface ◽  
Envelope Glycoprotein ◽  
Bovine Leukemia Virus ◽  
Virus Entry ◽  
Leukemia Virus ◽  
Cellular Receptor ◽  
Cationic Amino Acid Transporter ◽  
Cell Leukemia ◽  
Cationic Amino Acid ◽  
Human T Cell

AbstractBovine leukemia virus (BLV) is the causative agent of enzootic bovine leukosis, the most common neoplastic disease of cattle, which is closely related to human T-cell leukemia viruses. BLV has spread worldwide and causes a serious problem for the cattle industry. The cellular receptor specifically binds with viral envelope glycoprotein (Env) and this attachment mediates cell fusion to lead virus entry. BLV Env reportedly binds to cationic amino acid transporter 1 (CAT1)/SLC7A1, but whether the CAT1/SLC7A1 is an actual receptor for BLV remains unknown. Here, we showed that CAT1 functioned as an infection receptor, interacting with BLV particles. Cells expressing undetectable CAT1 levels were resistant to BLV infection but became highly susceptible upon CAT1 overexpression. CAT1 exhibited specific binding to BLV particles on the cell surface and co-localized with the Env in endomembrane compartments and membrane. Knockdown of CAT1 in permissive cells significantly reduced binding to BLV particles and BLV infection. In addition, bovine serum with neutralizing activity from a BLV-infected cattle inhibited BLV particles. Expression of CAT1 from various species demonstrated no species-specificity for BLV infection, implicating CAT1 as a functional BLV receptor responsible for its broad host range. These findings provide insights for BLV infection and for developing new strategies for treating BLV and preventing its spread.Author SummaryBovine leukemia virus (BLV), which can infect a variety of animal species and induce lymphoma in cattle, is a member of the familyRetroviridae. BLV induces huge economic losses by not only lymphoma but also subclinical forms of the disease. In addition, BLV is frequently used as an animal model of human T-cell leukemia virus (HTLV), as BLV has many similar characteristics to HTLV. Thus, understanding BLV pathogenesis contribute to resolve not only BLV-but also HTLV-induced problems. Retroviral envelope glycoprotein (Env) is specifically recognized by the cellular receptor at cell surface, which induces a conformational changes between viral and cell membrane to entry. Thus, the elucidation of cellular receptor for BLV infection is very important for virus entry. However, the BLV receptor has not been identified yet. In the current study, we found that BLV Env protein binds to cationic amino acid transporter 1 (CAT1)/SLC7A1 at cell surface, artificial expression of CAT1 in CAT1-negative cells confers the cells susceptible to BLV infection, and CAT1-silencing significantly reduces BLV infection, concluding that CAT1 is the BLV receptor. These findings will have far reaching great advantages of insights in the retrovirus study.

scholarly journals Similar Regulation of Cell Surface Human T-Cell Leukemia Virus Type 1 (HTLV-1) Surface Binding Proteins in Cells Highly and Poorly Transduced by HTLV-1-Pseudotyped Virions

2002 ◽  
Vol 76 (24) ◽  
pp. 12723-12734 ◽  
Author(s):  
Kathryn S. Jones ◽  
Manisha Nath ◽  
Cari Petrow-Sadowski ◽  
Andrea C. Baines ◽  
Megan Dambach ◽  
...  
Keyword(s):  
T Cell ◽  
Cell Surface ◽  
Cell Lines ◽  
Virus Type ◽  
Leukemia Virus ◽  
Cell Leukemia ◽  
Cell Leukemia Virus Type ◽  
Human T Cell ◽  
T Cell Leukemia Virus

ABSTRACT Little is known about the requirements for human T-cell leukemia virus type 1 (HTLV-1) entry, including the identity of the cellular receptor(s). Previous studies have shown that although the HTLV receptor(s) are widely expressed on cell lines of various cell types from different species, cell lines differ dramatically in their susceptibility to HTLV-Env-mediated fusion. Human cells (293, HeLa, and primary CD4+ T cells) showed higher levels of binding at saturation than rodent (NIH 3T3 and NRK) cells to an HTLV-1 SU immunoadhesin. A direct comparison of the binding of the HTLV-1 surface glycoprotein (SU) immunoadhesin and transduction by HTLV-1 pseudotyped virus revealed parallels between the level of binding and the titer for various cell lines. When cells were treated with phorbol myristate acetate (PMA), which down-modulates a number of cell surface molecules, the level of SU binding was markedly reduced. However, PMA treatment only slightly reduced the titer of murine leukemia virus(HTLV-1) on both highly susceptible and poorly susceptible cells. Treatment of target cells with trypsin greatly reduced binding, indicating that the majority of HTLV SU binding is to proteins. Polycations, which enhance the infectivity of several other retroviruses, inhibited HTLV-1 Env-mediated binding and entry on both human and rodent cells. These results suggest that factors other than the number of primary binding receptors are responsible for the differences in the titers of HTLV-1 pseudotypes between highly susceptible cells and poorly susceptible cells.

scholarly journals Bovine leukosis and the possibility to cause cancer in humans: A scientific review

2018 ◽  
Vol 42 (1) ◽  
pp. 52-60
Author(s):  
Huda Hameed Kadhim Alabbody
Keyword(s):  
Bovine Leukemia Virus ◽  
Human Cancer ◽  
Leukemia Virus ◽  
Cell Leukemia ◽  
Scientific Review ◽  
Enzootic Bovine Leukosis ◽  
Human T Cell ◽  
T Cell Leukemia Virus ◽  
Bovine Leukosis ◽  
Control And Eradication

    This review was made to explore the recent multiple studies on enzootic bovine leukosis, focusing on its prevalence, economic impact, the link with public health and the possibility to cause cancer in humans. The causative agent of enzootic bovine leukosis is a virus closely related to human T- cell leukemia virus (HTLV-1). The closeness between the two viruses helps the progress of cancer research in diagnosis and treatment, also the development of a vaccine in both human and veterinary medicine .The enzootic bovine leukosis is widely spread in the continents. The economic loses of enzootic bovine leukosis is related to the lowered productivity of effected cattle, morbidity, mortality and cost of control and eradication. This review proved that bovine leukemia virus is innocent from human cancer infection and there is no proof of virus living in human tissues. But this subject needs a lot of research to know the mechanism of the virus and its affects in cellular content of the organism.

scholarly journals Oncoviral Bovine Leukemia Virus G4 and Human T-Cell Leukemia Virus Type 1 p13II Accessory Proteins Interact with Farnesyl Pyrophosphate Synthetase

2002 ◽  
Vol 76 (3) ◽  
pp. 1400-1414 ◽  
Author(s):  
Laurent Lefèbvre ◽  
Alain Vanderplasschen ◽  
Vincenzo Ciminale ◽  
Hubertine Heremans ◽  
Olivier Dangoisse ◽  
...  
Keyword(s):  
Bovine Leukemia Virus ◽  
Leukemia Virus ◽  
Accessory Proteins ◽  
Farnesyl Pyrophosphate ◽  
Cell Leukemia ◽  
Cell Leukemia Virus Type ◽  
Human T Cell ◽  
T Cell Leukemia Virus ◽  
Α Helix

ABSTRACT G4 and p13II are accessory proteins encoded by the X region of bovine leukemia virus and human T-cell leukemia virus type 1 (HTLV-1), respectively. Disruption of the G4 and p13II open reading frames interferes with viral spread in animal model systems, indicating that the corresponding proteins play a key role in viral replication. In addition, G4 is oncogenic in primary cell cultures and is absolutely required for efficient onset of leukemogenesis in sheep. To gain insight into the function of these proteins, we utilized the yeast two-hybrid system to identify protein partners of G4. Results revealed that G4 interacts with farnesyl pyrophosphate synthetase (FPPS), a protein involved in the mevalonate/squalene pathway and in synthesis of FPP, a substrate required for prenylation of Ras. The specificity of the interaction was verified by glutathione S-transferase (GST) pull-down assays and by coimmunoprecipitation experiments. Furthermore, confocal microscopy showed that the subcellular localization of G4 was profoundly affected by FPPS. The G4 protein itself was not prenylated, at least in rabbit reticulocyte lysate-based assays. The domain of G4 required for binding to FPPS was restricted to an amphipathic α-helix rich in arginine residues. Subtle mutation of this α-helix abrogated G4 oncogenic potential in vitro, providing a biological relevance for FPPS-G4 complex formation in cells. Finally, HTLV-1 p13II was also found to specifically interact with FPPS (in yeast as well as in GST pull-down assays) and to colocalize with G4 in mitochondria, suggesting a functional analogy between these oncoviral accessory proteins. Identification of FPPS as a molecular partner for p13II and G4 accessory proteins opens new prospects for treatment of retrovirus-induced leukemia.

scholarly journals Deltaretroviruses have circulated since at least the Paleogene and infected a broad range of mammalian species

Retrovirology ◽  
2019 ◽  
Vol 16 (1) ◽  
Author(s):  
Tomáš Hron ◽  
Daniel Elleder ◽  
Robert J. Gifford
Keyword(s):  
Gene Regulation ◽  
Bovine Leukemia Virus ◽  
Fossil Record ◽  
Leukemia Virus ◽  
Mammalian Species ◽  
Endogenous Retroviruses ◽  
Cell Leukemia ◽  
Coding Regions ◽  
Human T Cell ◽  
Leukemia Viruses

AbstractThe Deltaretrovirus genus of retroviruses (family Retroviridae) includes the human T cell leukemia viruses and bovine leukemia virus (BLV). Relatively little is known about the biology and evolution of these viruses, because only a few species have been identified and the genomic ‘fossil record’ is relatively sparse. Here, we report the discovery of multiple novel endogenous retroviruses (ERVs) derived from ancestral deltaretroviruses. These sequences—two of which contain complete or near complete internal coding regions—reside in genomes of several distinct mammalian orders, including bats, carnivores, cetaceans, and insectivores. We demonstrate that two of these ERVs contain unambiguous homologs of the tax gene, indicating that complex gene regulation has ancient origins within the Deltaretrovirus genus. ERVs demonstrate that the host range of the deltaretrovirus genus is much more extensive than suggested by the relatively small number of exogenous deltaretroviruses described so far, and allow the evolutionary timeline of deltaretrovirus-mammal interaction to be more accurately calibrated.

scholarly journals Human T-Cell Leukemia Virus Type 1 Envelope Glycoprotein gp46 Interacts with Cell Surface Heparan Sulfate Proteoglycans

2003 ◽  
Vol 77 (18) ◽  
pp. 9922-9930 ◽  
Author(s):  
Josefina D. Piñon ◽  
P. J. Klasse ◽  
Sushma R. Jassal ◽  
Sandy Welson ◽  
Jonathan Weber ◽  
...  
Keyword(s):  
Envelope Glycoprotein ◽  
Dextran Sulfate ◽  
Leukemia Virus ◽  
Pseudotyped Virus ◽  
Target Cells ◽  
Cell Leukemia ◽  
Cell Leukemia Virus Type ◽  
Human T Cell ◽  
T Cell Leukemia Virus

ABSTRACT The major receptors required for attachment and entry of the human T-cell leukemia virus type 1 (HTLV-1) remain to be identified. Here we demonstrate that a functional, soluble form of the HTLV-1 surface envelope glycoprotein, gp46, fused to an immunoglobulin Fc region (gp46-Fc) binds to heparan sulfate proteoglycans (HSPGs) on mammalian cells. Substantial binding of gp46-Fc to HeLa and Chinese hamster ovary (CHO) K1 cells that express HSPGs was detected, whereas binding to the sister CHO lines 2244, which expresses no HSPGs, and 2241, which expresses no glycosaminoglycans (GAGs), was much reduced. Enzymatic removal of HSPGs from HeLa and CHO K1 cells also reduced gp46-Fc binding. Dextran sulfate inhibited gp46-Fc binding to HSPG-expressing cells in a dose-dependent manner, whereas chondroitin sulfate was less effective. By contrast, dextran sulfate inhibited gp46-Fc binding to GAG-negative cells such as CHO 2244, CHO 2241, and Jurkat T cells weakly or not at all. Dextran sulfate inhibited HTLV-1 envelope glycoprotein (Env)-pseudotyped virus infection of permissive, HSPG-expressing target cells and blocked syncytium formation between HTLV-1 Env-expressing cells and HSPG-expressing permissive target cells. Finally, HSPG-expressing cells were more permissive for HTLV-1 Env-pseudotyped virus infection than HSPG-negative cells. Thus, similar to other pathogenic viruses, HTLV-1 may have evolved to use HSPGs as cellular attachment receptors to facilitate its propagation.

Sign in / Sign up

Export Citation Format

Share Document