The mouse mammary tumor virus (MMTV) is a retrovirus that causes mammary tumors in mice. During lactation, it is secreted into the milk which infects the pups; it also reinfects the dam's mammary epithelium, thereby increasing its chances of integrating near a protooncogene and producing transformation. Therefore, both the initial infection and reinfection are of primary importance in MMTV-induced tumorigenesis and they are both mediated by a cell surface receptor. It is the specific aim of this project to characterize the MMTV receptor with respect to physiochemical properties, histological localization, regulation and metabolism. The working hypotheses include the following: l) both MMTV receptor number and polarity will be related to the ability and route of tissue infection; 2) the mammary gland receptor will be closely related, if not identical, to the liver receptor; and 3) because these receptors probably serve an important role in mammary gland development and physiology, they will be widely distributed evolutionarily. To test these hypotheses, an in vitro infection system for MMTV has been developed in this laboratory and will be used to correlate receptor levels with infectivity. Receptor localization and metabolism will be studied by immunohistochemistry using antiserum developed against the liver MMTV binding protein. The mammary gland receptor will also be isolated, since viral receptors in different tissues may not be identical. These studies will be done with C3H mice (Mus); however, MMV binding activity has also been demonstrated on deer mouse (Peromyscus) epithelial cells. Therefore, this distant species will be used to investigate the nature and functionality of this receptor. This project is related to biomedical research in that it will give insights to how viruses can exploit plasma membrane proteins in order to initiate infec- tion. In particular, the MMTV system shares many important characteristics with several other oncoviruses closely related to human cancers, such as the human papilloma virus (cervical cancer), the human immunodeficiency virus (Kaposi's sarcoma) and the human T-cell leukemia virus. This may lead to better strategies for blocking these viruses at the point of infection.
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