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A novel murine oncornavirus with dual eco- and xenotropic properties
Abstract:
Infection of Swiss mouse 3T3FL cells with a clonal isolate of Moloney leukemia virus (MLV-IC) resulted in virus progeny composed of at least three different murine helper oncornaviruses. Each entity was purified in appropriate cells by several sequential terminal dilution isolations and was grouwn to high titers. Besides ecotropic MLV-IC there was a pure xenotropic virus and a third novel virus with properties of both eco- and xenotropic viruses. The purified xenotropic virus had a wide host range, was restricted in mouse cells, and was inactivated by normal mouse sera like other xenotropic isolates. The purified virus with hybrid properties (HIX) could infect a wide range of mammalian cells, which included both N and B mouse cells. HIX gave single-hit titrations with equal titers on both mouse and cat indicator cells. Envelope properties of HIX were examined by virus preinfection interference, by interference involving viral glycoprotein, and by neutralization with specific antisera. Both xenotropic and MLV-IC type ecotropic determinants were found on the virus coat. The origins of HIX and the xenotropic virus were investigated in detail. The original MLV-IC stock had HIX type virus in low titer but no detectable pure xenotropic virus. Infection of mouse cells with a single infectious unit of the ecotropic virus from the MLV-IC virus stocks could at times give rise to HIX type virus. HIX type virus, passed once through heterologous rat cells, was subjected to long-term passage either in infected mouse or cat cells. After several months HIX type virus disappeared from some mouse and cat cell systems. The possible hybrid nature of HIX and the origins of newly appearing xenotropic viruses are discussed.
Insights
Moloney leukemia virus (MLV-IC) infection yields ecotropic, xenotropic, and novel hybrid murine leukemia viruses. The hybrid virus (HIX) exhibits dual tropism and mixed envelope properties, with origins linked to MLV-IC.
Area of Science:
- Virology
- Molecular Biology
- Oncornaviruses
Background:
- Moloney leukemia virus (MLV-IC) is a murine helper oncornavirus.
- Viral progeny composition can be complex and heterogeneous.
- Understanding viral tropism and origins is crucial for virology research.
Purpose of the Study:
- To characterize the viral progeny resulting from MLV-IC infection of Swiss mouse 3T3FL cells.
- To purify and define the properties of different viral entities, including a novel hybrid virus.
- To investigate the origins and potential hybrid nature of these murine leukemia viruses.
Main Methods:
- Sequential terminal dilution isolations to purify viral entities.
- High-titer virus growth in appropriate cell lines.
- Host range determination, including infection of mouse and cat cells.
- Envelope property analysis via interference assays and neutralization with antisera.
- Investigation of viral origins through infection experiments and serial passage.
Main Results:
- MLV-IC infection produced ecotropic, xenotropic, and a novel hybrid virus (HIX).
- The purified xenotropic virus showed restricted tropism in mouse cells.
- The HIX virus displayed broad mammalian cell tropism, infecting both N and B mouse cells, and possessed dual ecotropic and xenotropic envelope determinants.
- HIX was present at low titer in the original MLV-IC stock, and could arise from infection with ecotropic MLV-IC.
- HIX virus disappeared from some mouse and cat cell systems after prolonged passage.
Conclusions:
- MLV-IC infection can generate a diverse array of murine leukemia viruses, including a hybrid with mixed tropism.
- The hybrid virus (HIX) likely arises from recombination events or genetic reassortment.
- The findings shed light on the origins of xenotropic viruses and the potential for generating novel viral variants.