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Abstract:
An immunological focus assay using monoclonal antibodies on live adherent in vitro cell lines was employed to detect and isolate different types of murine leukemia viruses (MuLVs) from spleen and thymus cells of young (less than 1 month of age) AKR/J mice. In agreement with earlier studies, ecotropic viruses were detected from cells of both tissues in all mice tested, although only trace levels of ecotropic MuLV infectious centers were found with thymus cells from mice of this age. Polytropic MuLVs were not detected in mice less than 3 weeks of age; however, between the ages of 3 and 4 weeks, polytropic viruses were detectable in assays of spleen cells from 50% of the mice. No polytropic MuLVs were detected in assays of thymocytes from any mice of this age. Several polytropic MuLVs obtained from spleens of young mice were further characterized. All of the isolates were infectious for both mink and SC-1 (feral mouse) cells, and exhibited interference properties typical of polytropic MuLVs. However, none of the viruses induced obvious cytopathic effects (CPE) on mink cells. All of the viruses appeared antigenically similar with regard to their reactivities to a panel of 12 monoclonal antibodies directed at envelope antigens of polytropic MuLVs. RNase T1-resistant oligonucleotide analysis of a polytropic MuLV from a 26-day-old mouse indicated that its entire env gene was derived from nonecotropic sequences while the remainder of its genome was indistinguishable from the ecotropic parent. The isolate thus exhibited a genome structure typical of Class II polytropic MuLVs and is the first example of this type of MuLV isolated from AKR/J mice. Examination of polytropic MuLVs derived from the spleens and thymuses of 5- to 6-month-old mice indicated that only 2 of 10 isolates examined induced CPE on mink cells. Furthermore, most of the CPE-negative viruses isolated from spleen and thymus cells of these mice exhibited in vitro host ranges and antigenic reactivities similar to isolates from young mice, suggesting that this type of polytropic MuLV may originate in the spleen, subsequently spread to other tissues, and persist throughout the preleukemic period. The detection of polytropic viruses in a large proportion of very young mice is in contrast to previous studies which have not detected polytropic virus production in AKR mice less than 5 to 6 months of age.(ABSTRACT TRUNCATED AT 250 WORDS)
Insights
This study detected polytropic murine leukemia viruses (MuLVs) in young AKR/J mice, challenging previous findings. These viruses appear to originate in the spleen and persist, suggesting an earlier role in preleukemia than previously understood.
Area of Science:
- Virology
- Immunology
- Mouse Models of Disease
Background:
- Murine leukemia viruses (MuLVs) are retroviruses implicated in various mouse diseases.
- Previous studies indicated polytropic MuLVs appear later in AKR/J mice, typically after 5-6 months of age.
- The early detection and characterization of MuLVs in young mice are crucial for understanding leukemogenesis.
Purpose of the Study:
- To detect and isolate different types of MuLVs from young AKR/J mice using an immunological focus assay.
- To characterize polytropic MuLV isolates from young mice, including their host range, antigenic properties, and genome structure.
- To investigate the potential origin and persistence of polytropic MuLVs during the preleukemic period.
Main Methods:
- Immunological focus assay with monoclonal antibodies on live adherent in vitro cell lines.
- Isolation and characterization of MuLVs from spleen and thymus cells of young AKR/J mice (less than 1 month old).
- Analysis of viral host range, interference properties, antigenicity, and genome structure (RNase T1-resistant oligonucleotide analysis).
Main Results:
- Ecotropic MuLVs were detected in all tested mice, while polytropic MuLVs were first detected in spleen cells of 50% of mice aged 3-4 weeks.
- Polytropic MuLV isolates from young mice were infectious for mink and SC-1 cells, showed typical interference, but no cytopathic effects (CPE) on mink cells.
- Genomic analysis revealed an isolate with an env gene from nonecotropic sequences, typical of Class II polytropic MuLVs, marking the first isolation from AKR/J mice.
Conclusions:
- Polytropic MuLVs can be detected in very young AKR/J mice, contradicting previous findings of later onset.
- These viruses may originate in the spleen and persist throughout the preleukemic period, potentially influencing disease progression.
- The early detection of Class II polytropic MuLVs in AKR/J mice provides new insights into MuLV-induced leukemogenesis.