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Distribution of Fv-4 resistant gene product in Friend leukemia virus-resistant Fv-4r mouse strain
M Kitagawa1, S Aizawa, H Kamisaku
1Department of Pathology and Immunology, Faculty of Medicine, Tokyo Medical and Dental University, Japan.
Abstract:
Fv-4 is a mouse gene that dominantly confers resistance to infection by ecotropic murine leukemia virus (MuLV). We demonstrated previously that the Fv-4 resistant (Fv-4r) gene product, Fv-4r env antigen, is released from Fv-4r-bearing BALB/c-Fv-4Wr (C4W) mouse-derived cells into serum in vivo and binds to cells expressing surface receptors for ecotropic MuLV, thereby protecting them from infection with Friend leukemia virus (FLV) by receptor interference. This unique resistance mechanism against retroviral infection might provide a possible therapeutic model system of human retroviral infection such as AIDS. To further investigate the Fv-4r gene action in vivo, we examined the distribution and character of Fv-4r env antigen in serum and systemic organs from C4W mice. The Fv-4r env antigen was immunohistochemically localized to the lympho-hematopoietic cells and exocrine glandular cells, such as those of the salivary gland and pancreas. Using immunoprecipitation followed by Western blotting, we determined two types of gp70-related Fv-4r env antigen in the serum of C4W mice, showing molecular weights of either 70-75 kDa and 80-85 kDa. When thymocytes from Fv-4 susceptible gene (Fv-4r)-bearing C3H mouse were mixed with C4W mouse serum, the 70-75k Da molecule of the C4W serum dominantly bound to C3H thymocytes and thus contributed to receptor interference function. Using immunoelectron microscopy, Fv-4r env antigen was mainly localized to the cell surface membrane of thymic lymphoid cells, while acinar cells of the salivary gland possessed Fv-4r env antigen in the endoplasmic reticulum (ER) as well as on the cell surface membrane. These data indicate that several glandular organs, as well as lymphohematopoietic organs of C4W mice, may contribute to the production of cell-free Fv-4r env antigen, resulting in protection of cells from infection with FLV by receptor interference.
Insights
The Fv-4 resistant gene in mice produces an env antigen that circulates in serum, protecting cells from retroviral infection via receptor interference. This mechanism, observed in lympho-hematopoietic and glandular cells, offers a potential therapeutic model for human retroviral infections like AIDS.
Area of Science:
- Immunology
- Virology
- Genetics
Background:
- The Fv-4 gene confers dominant resistance to ecotropic murine leukemia virus (MuLV) infection in mice.
- The Fv-4 resistant (Fv-4r) gene product, Fv-4r env antigen, is released into serum and protects cells via receptor interference.
- This mechanism presents a potential model for therapeutic strategies against human retroviral infections such as AIDS.
Purpose of the Study:
- To investigate the in vivo action of the Fv-4r gene.
- To determine the distribution and characteristics of Fv-4r env antigen in serum and systemic organs of C4W mice.
Main Methods:
- Immunohistochemistry to localize Fv-4r env antigen.
- Immunoprecipitation and Western blotting to characterize serum antigen.
- In vitro binding assays with thymocytes.
- Immunoelectron microscopy to examine cellular localization.
Main Results:
- Fv-4r env antigen localized to lympho-hematopoietic and glandular cells (salivary gland, pancreas).
- Two types of gp70-related Fv-4r env antigen (70-75 kDa and 80-85 kDa) identified in serum.
- The 70-75 kDa antigen bound to susceptible thymocytes, mediating receptor interference.
- Antigen found on cell surface membranes of thymic cells and in ER/cell surface of salivary gland acinar cells.
Conclusions:
- Glandular and lymphohematopoietic organs contribute to cell-free Fv-4r env antigen production.
- This antigen protects against Friend leukemia virus (FLV) infection through receptor interference.
- The Fv-4r resistance mechanism provides insights into retroviral infection control.