scholarly journals Binding of Murine Leukemia Virus Gag Polyproteins to KIF4, a Microtubule-Based Motor Protein

1998 ◽  
Vol 72 (8) ◽  
pp. 6898-6901 ◽  
Author(s):  
Wankee Kim ◽  
Yao Tang ◽  
Yasushi Okada ◽  
Ted A. Torrey ◽  
Sisir K. Chattopadhyay ◽  
...  
Keyword(s):  
Murine Leukemia Virus ◽  
Mammalian Cells ◽  
Leukemia Virus ◽  
Motor Protein ◽  
Cellular Protein ◽  
Gag Proteins ◽  
C Terminus ◽  
Murine Leukemia

ABSTRACT A cDNA clone encoding a cellular protein that interacts with murine leukemia virus (MuLV) Gag proteins was isolated from a T-cell lymphoma library. The sequence of the clone is identical to the C terminus of a cellular protein, KIF4, a microtubule-associated motor protein that belongs to the kinesin superfamily. KIF4-MuLV Gag associations have been detected in vitro and in vivo in mammalian cells. We suggest that KIF4 could be involved in Gag polyprotein translocation from the cytoplasm to the cell membrane.

Heterogeneity of Murine Leukemia Virus in vitro DNA; Detection of Viral DNA in Mammalian Cells

Science ◽  
1971 ◽  
Vol 172 (3990) ◽  
pp. 1353-1355 ◽  
Author(s):  
L. D. Gelb ◽  
S. A. Aaronson ◽  
M. A. Martin
Keyword(s):  
Murine Leukemia Virus ◽  
Mammalian Cells ◽  
Dna Detection ◽  
Leukemia Virus ◽  
Viral Dna ◽  
Murine Leukemia

Strong selection for cells containing new ecotropic recombinant murine leukemia virus provirus after propagation of C57BL/6 radiation-induced thymoma cells in vitro or in vivo

1983 ◽  
Vol 3 (9) ◽  
pp. 1675-1679
Author(s):  
P Jolicoeur ◽  
E Rassart ◽  
P Sankar-Mistry
Keyword(s):  
Cell Lines ◽  
Murine Leukemia Virus ◽  
Leukemia Virus ◽  
Primary Radiation ◽  
Secondary Tumors ◽  
Radiation Induced ◽  
Viral Sequences ◽  
Murine Leukemia

Using the Southern procedure, we have studied the presence of ecotropic-specific murine leukemia viral sequences in genomic DNA isolated from primary X-ray-induced thymomas, from lymphoid cell lines established from them, or from secondary tumors passaged in vivo. We found that primary radiation-induced thymomas and infiltrated spleens do not harbor newly acquired ecotropic provirus. However, additional ecotropic proviruses (which appear recombinant in the gagpol region) could be detected in most of the tumorigenic cell lines established in vitro from them and in tumors arising from subcutaneous transplantation of the primary thymomas. These results suggest that primary radiation-induced thymomas may not be clonal. They also indicate a strong correlation between the presence of ecotropic recombinant proviruses in the genome and the growth ability, both in vitro and in vivo, of specific cells within these thymomas, suggesting a possible mitogenic function for murine leukemia virus.

scholarly journals Murine Leukemia Virus P50 Protein Counteracts APOBEC3 by Blocking Its Packaging

2020 ◽  
Vol 94 (18) ◽  
Author(s):  
Wenming Zhao ◽  
Charbel Akkawi ◽  
Marylène Mougel ◽  
Susan R. Ross
Keyword(s):  
Cell Line ◽  
Murine Leukemia Virus ◽  
Leukemia Virus ◽  
Stable Cell Line ◽  
Host Restriction ◽  
C Terminus ◽  
Alternatively Spliced ◽  
Apobec3 Proteins ◽  
Murine Leukemia

ABSTRACT Apolipoprotein B editing enzyme, catalytic polypeptide 3 (APOBEC3) family members are cytidine deaminases that play important roles in intrinsic responses to retrovirus infection. Complex retroviruses like human immunodeficiency virus type 1 (HIV-1) encode the viral infectivity factor (Vif) protein to counteract APOBEC3 proteins. Vif induces degradation of APOBEC3G and other APOBEC3 proteins and thereby prevents their packaging into virions. It is not known if murine leukemia virus (MLV) encodes a Vif-like protein. Here, we show that the MLV P50 protein, produced from an alternatively spliced gag RNA, interacts with the C terminus of mouse APOBEC3 and prevents its packaging without causing its degradation. By infecting APOBEC3 knockout (KO) and wild-type (WT) mice with Friend or Moloney MLV P50-deficient viruses, we found that APOBEC3 restricts the mutant viruses more than WT viruses in vivo. Replication of P50-mutant viruses in an APOBEC3-expressing stable cell line was also much slower than that of WT viruses, and overexpressing P50 in this cell line enhanced mutant virus replication. Thus, MLV encodes a protein, P50, that overcomes APOBEC3 restriction by preventing its packaging into virions. IMPORTANCE MLV has existed in mice for at least a million years, in spite of the existence of host restriction factors that block infection. Although MLV is considered a simple retrovirus compared to lentiviruses, it does encode proteins generated from alternatively spliced RNAs. Here, we show that P50, generated from an alternatively spliced RNA encoded in gag, counteracts APOBEC3 by blocking its packaging. MLV also encodes a protein, glycoGag, that increases capsid stability and limits APOBEC3 access to the reverse transcription complex (RTC). Thus, MLV has evolved multiple means of preventing APOBEC3 from blocking infection, explaining its survival as an infectious pathogen in mice.

scholarly journals Bromo- and Extraterminal Domain Chromatin Regulators Serve as Cofactors for Murine Leukemia Virus Integration

2013 ◽  
Vol 87 (23) ◽  
pp. 12721-12736 ◽  
Author(s):  
Saumya Shree Gupta ◽  
Tobias Maetzig ◽  
Goedele N. Maertens ◽  
Azar Sharif ◽  
Michael Rothe ◽  
...  
Keyword(s):  
Murine Leukemia Virus ◽  
Leukemia Virus ◽  
Retroviral Vectors ◽  
Transcription Start ◽  
Preintegration Complex ◽  
Transcription Start Sites ◽  
Bet Inhibitors ◽  
Murine Leukemia

Retroviral integrase (IN) proteins catalyze the permanent integration of proviral genomes into host DNA with the help of cellular cofactors. Lens epithelium-derived growth factor (LEDGF) is a cofactor for lentiviruses, including human immunodeficiency virus type 1 (HIV-1), and targets lentiviral integration toward active transcription units in the host genome. In contrast to lentiviruses, murine leukemia virus (MLV), a gammaretrovirus, tends to integrate near transcription start sites. Here, we show that the bromodomain and extraterminal domain (BET) proteins BRD2, BRD3, and BRD4 interact with gammaretroviral INs and stimulate the catalytic activity of MLV INin vitro. We mapped the interaction site to a characteristic structural feature within the BET protein extraterminal (ET) domain and to three amino acids in MLV IN. The ET domains of different BET proteins stimulate MLV integrationin vitroand, in the case of BRD2, alsoin vivo. Furthermore, two small-molecule BET inhibitors, JQ1 and I-BET, decrease MLV integration and shift it away from transcription start sites. Our data suggest that BET proteins might act as chromatin-bound acceptors for the MLV preintegration complex. These results could pave a way to redirecting MLV DNA integration as a basis for creating safer retroviral vectors.

scholarly journals R-Peptide Cleavage Potentiates Fusion-Controlling Isomerization of the Intersubunit Disulfide in Moloney Murine Leukemia Virus Env

2007 ◽  
Vol 82 (5) ◽  
pp. 2594-2597 ◽  
Author(s):  
Robin Löving ◽  
Kejun Li ◽  
Michael Wallin ◽  
Mathilda Sjöberg ◽  
Henrik Garoff
Keyword(s):  
Murine Leukemia Virus ◽  
Leukemia Virus ◽  
Moloney Murine Leukemia Virus ◽  
Isomerization Reaction ◽  
Peptide Cleavage ◽  
In Vivo Assays ◽  
Env Protein ◽  
Murine Leukemia

ABSTRACT Fusion of the membrane of the Moloney murine leukemia virus (Mo-MLV) Env protein is facilitated by cleavage of the R peptide from the cytoplasmic tail of its TM subunit, but the mechanism for this effect has remained obscure. The fusion is also controlled by the isomerization of the intersubunit disulfide of the Env SU-TM complex. In the present study, we used several R-peptide-cleavage-inhibited virus mutants to show that the R peptide suppresses the isomerization reaction in both in vitro and in vivo assays. Thus, the R peptide affects early steps in the activation pathway of murine leukemia virus Env.

scholarly journals Targeting of Murine Leukemia Virus Gag to the Plasma Membrane Is Mediated by PI(4,5)P2/PS and a Polybasic Region in the Matrix

2009 ◽  
Vol 84 (1) ◽  
pp. 503-515 ◽  
Author(s):  
E. Hamard-Peron ◽  
F. Juillard ◽  
J. S. Saad ◽  
C. Roy ◽  
P. Roingeard ◽  
...  
Keyword(s):  
Human Immunodeficiency Virus ◽  
Plasma Membrane ◽  
Murine Leukemia Virus ◽  
Leukemia Virus ◽  
Gag Proteins ◽  
Immunodeficiency Virus ◽  
The Matrix ◽  
Polybasic Region ◽  
Murine Leukemia

ABSTRACT Membrane targeting of the human immunodeficiency virus Gag proteins is dependent on phosphatidylinositol-(4,5)-bisphosphate [PI(4,5)P2] located in the plasma membrane. In order to determine if evolutionarily distant retroviral Gag proteins are targeted by a similar mechanism, we generated mutants of the matrix (MA) domain of murine leukemia virus (MuLV) Gag, examined their binding to membrane models in vitro, and analyzed their phenotypes in cell culture. In vitro, we showed that MA bound all the phosphatidylinositol phosphates with significant affinity but displayed a strong specificity for PI(4,5)P2 only if enhanced by phosphatidylserine. Mutations in the polybasic region in MA dramatically reduced this affinity. In cells, virus production was strongly impaired by PI(4,5)P2 depletion under conditions of 5ptaseIV overexpression, and mutations in the MA polybasic region altered Gag localization, membrane binding, and virion production. Our results suggest that the N-terminal polybasic cluster of MA is essential for Gag targeting to the plasma membrane. The binding of the MA domain to PI(4,5)P2 appears to be a conserved feature among retroviruses despite the fact that the MuLV-MA domain is structurally different from that of human immunodeficiency virus types 1 and 2 and lacks a readily identifiable PI(4,5)P2 binding cleft.

scholarly journals SERINC5 Potently Restricts Retrovirus Infection In Vivo

mBio ◽  
2020 ◽  
Vol 11 (4) ◽  
Author(s):  
Uddhav Timilsina ◽  
Supawadee Umthong ◽  
Brian Lynch ◽  
Aimee Stablewski ◽  
Spyridon Stavrou
Keyword(s):  
Murine Leukemia Virus ◽  
Leukemia Virus ◽  
Viral Envelope ◽  
The Other ◽  
Immunodeficiency Virus ◽  
Retrovirus Infection ◽  
Hiv 1 ◽  
Murine Leukemia

ABSTRACT The serine incorporator (SERINC) proteins are multipass transmembrane proteins that affect sphingolipid and phosphatidylserine synthesis. Human SERINC5 and SERINC3 were recently shown to possess antiretroviral activity for a number of retroviruses, including human immunodeficiency virus (HIV), murine leukemia virus (MLV), and equine infectious anemia virus (EIAV). In the case of MLV, the glycosylated Gag (glyco-Gag) protein was shown to counteract SERINC5-mediated restriction in in vitro experiments and the viral envelope was found to determine virion sensitivity or resistance to SERINC5. However, nothing is known about the in vivo function of SERINC5. Antiretroviral function of a host factor in vitro is not always associated with antiretroviral function in vivo. Using SERINC5−/− mice that we had generated, we showed that mouse SERINC5 (mSERINC5) restriction of MLV infection in vivo is influenced not only by glyco-Gag but also by the retroviral envelope. Finally, we also examined the in vivo function of the other SERINC gene with known antiretroviral functions, SERINC3. By using SERINC3−/− mice, we found that the murine homologue, mSERINC3, had no antiretroviral role either in vivo or in vitro. To our knowledge, this report provides the first data showing that SERINC5 restricts retrovirus infection in vivo and that restriction of retrovirus infectivity in vivo is dependent on the presence of both glyco-Gag and the viral envelope. IMPORTANCE This study examined for the first time the in vivo function of the serine incorporator (SERINC) proteins during retrovirus infection. SERINC3 and SERINC5 (SERINC3/5) restrict a number of retroviruses, including human immunodeficiency virus 1 (HIV-1) and murine leukemia virus (MLV), by blocking their entry into cells. Nevertheless, HIV-1 and MLV encode factors, Nef and glycosylated Gag, respectively, that counteract SERINC3/5 in vitro. We recently developed SERINC3 and SERINC5 knockout mice to examine the in vivo function of these genes. We found that SERINC5 restriction is dependent on the absence of glycosylated Gag and the expression of a specific viral envelope glycoprotein. On the other hand, SERINC3 had no antiviral function. Our findings have implications for the development of therapeutics that target SERINC5 during retrovirus infection.

scholarly journals Effect of Host Modification and Age on Airway Epithelial Gene Transfer Mediated by a Murine Leukemia Virus-Derived Vector

1998 ◽  
Vol 72 (11) ◽  
pp. 8861-8872 ◽  
Author(s):  
Larry G. Johnson ◽  
Jennifer P. Mewshaw ◽  
Hong Ni ◽  
Theodore Friedmann ◽  
Richard C. Boucher ◽  
...  
Keyword(s):  
Gene Transfer ◽  
Murine Leukemia Virus ◽  
Leukemia Virus ◽  
Brdu Incorporation ◽  
Transduction Efficiency ◽  
Airway Epithelial ◽  
Murine Leukemia ◽  
Airway Cells

ABSTRACT To study retroviral gene transfer to airway epithelia, we used a transient transfection technique to generate high titers (∼109 infectious units/ml after concentration) of murine leukemia virus (MuLV)-derived vectors pseudotyped with the vesicular stomatitis virus envelope glycoprotein (VSV-G). Transformed (CFT1) and primary airway epithelial cells were efficiently transduced by a VSV-G-pseudotyped lacZ vector (HIT-LZ) in vitro. CFT1 cells and primary cystic fibrosis (CF) airway cell monolayers infected with a vector (HIT-LCFSN) containing human CF transmembrane conductance regulator (CFTR) in the absence of selection expressed CFTR, as assessed by Western blot analysis, and exhibited functional correction of CFTR-mediated Cl− secretion. In vitro studies of persistence suggested that pseudotransduction was not a significant problem with our vector preparations. In a sulfur dioxide (SO2) inhalational injury model, bromodeoxyuridine (BrdU) incorporation rates were measured and found to exceed 50% in SO2-injured murine tracheal epithelium. HIT-LZ vector (multiplicity of infection of ∼10) instilled into the SO2-injured tracheas of anesthetized mice transduced 6.1% ± 1.3% of superficial airway cells in tracheas of weanling mice (3 to 4 weeks old; n = 10), compared to 1.4 ± 0.9% in mice 5 weeks of age (n = 4) and 0.2% in mice older than 6 weeks (n = 15). No evidence for gene transfer following delivery of HIT-LZ to tracheas of either weanling or older mice not injured with SO2 was detected. Because only a small fraction of BrdU-labeled airway cells were transduced, we examined the stability of the vector. No significant loss of vector infectivity over intervals (2 h) paralleling those of in vivo protocols was detected in in vitro assays using CFT1 cells. In summary, high-titer vectors permitted complementation of defective CFTR-mediated Cl− transport in CF airway cells in vitro without selection and demonstrated that the age of the animal appeared to be a major factor affecting in vivo retroviral transduction efficiency.

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