Moloney Strain Of Murine Sarcoma Virus Research Articles

Antipyretic and Antiviral Action of Vitamin A in Moloney Sarcoma Virus- and Poxvirus-Inoculated Mice 2

Six week-old male CBA/J mice fed a commercial powdered laboratory chow or the same chow supplemented with vitamin A palmitate (150,000 U/kg) were inoculated with either the Moloney strain of murine sarcoma virus (M-MuSV) or poxvirus. Central body temperature was measured daily. Both viruses elicited fevers, but the fevers were less pronounced and of shorter duration in the mice ingesting the vitamin A-supplemented diet. Palpable M-MuSV-induced tumors appeared later, were less frequent, grew more slowly, and were resorbed sooner in the mice fed the vitamin A supplement. Similarly, in these mice the appearance of pox lesions was delayed, their numbers reduced, and their disappearance hastened.

Inhibition of Cell-Mediated Cytotoxicity Against Tumor-Associated Antigens by Suppressor Cells From Tumor-Bearing Mice

Spleen cells from mice bearing primary tumours induced by Moloney strain of murine sarcoma virus (M-MuSV) strongly inhibited the in vitro generation of specific secondary cell-mediated cytotoxic response of spleen cells from M-MusV regressor mice. These suppressor cells were resistant to treatment with anti-theta serum and complement or to X-irradiation. It appeared that suppressor cells may have had a role in limiting the host's immune response against tumor growth.

Immune Reactivity in the Moloney Strain of Murine Sarcoma Virus Oncogenesis: Requirement of Thymus-Derived Lymphocytes for In Vivo Protection 2

To study the function of different lymphocyte populations in the Moloney strain of murine sarcoma virus (M-MuSV) tumorigenesis, we gave M-MuSV injections to CBA mice selectively deprived of thymus (T) lymphocytes by thymectomy, X-rradiation, and syngeneic bone marrow injection. Although no tumors appeared in the control group, 80% of the derived mice had tumors that grew progressively and ultimately killed them. In deprived mice, grafted with a syngeneic thymus (reconstituted mice) before or after an M-MuSV injection, tumors regressed or did not develop. Histologically, the lymph nodes and spleens of reconstituted mice, compared to those of deprived animals, showed repopulation of the thymus-dependent areas and prominent follicles in the cortex. Moreover, tumor tissue of reconstituted mice was extensively infiltrated by lymphocytes. To evaluate the number of lymphoid cells needed to prevent or regress M-MuSV tumors, we injected varying amounts of lymphoid cells into deprived mice. Even low lymphocyte numbers (10(6) cells) were sufficient to exert, in some cases, protection against M-MuSV tumorigenesis. This effect was not abolished by subsequent splenectomy or antilymphocyte serum treatment. Finally, deprived mice, given repeated injections of antiserum (hyperimmune) against M-MuSV, had tumors which appeared only after a prolonged latency. From these results, it is concluded that T-cell population integrity is important in affording total host protection against the M-MuSV tumors.

Tumor induction by Moloney sarcoma virus in athymic nude mice.

Athymic nude (nu/nu) mice, normal NMRI (plus/plus) mice, and nu/plus heterozygotes, inoculated at birth with the Moloney strain of murine sarcoma virus (M-MSV), did not differ either in tumor growth rate or incidence or in mortality due to tumor development; neither did nude (nu/nu) and normal NMRI mice inoculated with M-MSV at 30 days of age differ in the initial tumor growth rate. However, tumors induced in adult nude mice grew progressively and eventually killed the hosts, whereas tumors induced in adult normal NMRI mice completely regressed. These results indicated that thymus-dependent immunity, though not active in M-MSV tumor induction, determined whether the tumor, once formed, would regress or kill the host.

Murine virus-induced proteins synthesized by hamster tumor cells transformed by, but not producing, murine sarcoma virus.

The 8303 hamster tumor cells transformed by Moloney strain of murine sarcoma virus (M-MSV), but which do not produce virus, do contain murine virus-induced proteins. The virus-induced proteins within the cell were identified either as free proteins or in association with membranous material, including the plasma membrane. In addition, some were excreted by the 8303 hamster tumor cells into the growth medium. Most virus-induced proteins were larger than 68,000 daltons, and they did not dissociate into components of smaller size in the presence of detergent and a reducing agent. A small amount of virus-induced protein with a molecular weight of less than 20,000 was also found in the hamster tumor cells. No virus-specific proteins with the identical antigenic specificity or size of the major internal group specific antigen (molecular weight about 30,000) of the murine leukemia viruses were present in these cells. There is a common cell surface antigen present in three other tumor cell lines, both virus-producing and non-virus-producing, identical in reactivity to that of the murine virus-induced antigen of the 8303 hamster tumor cell. This antigen is not present on the cell surface of normal mouse embryo cells.

Effect of chlorite-oxidized oxyamylose on Moloney sarcoma virus-induced tumor formation in mice

Chlorite-oxidized oxyamylose (COAM) effectively inhibited tumor growth in NMRI mice infected neonatally with the Moloney strain of murine sarcoma virus (M-MSV). This protective effect was most pronounced with single doses of the compound administered shortly before or after virus challenge. At the appropriate dosage level, COAM was also effective when it was administered as a single dose at 7 or 13 days after the virus or when it was injected in repeated doses on alternate days from 7 till 19 days or from 13 till 23 days after virus challenge. COAM reduced both tumor incidence and death due to tumor growth. However, with the treatment regimens used, it did not cause a regression of tumors which had already appeared at the time treatment was initiated.

Retention of antigen specificity of murine sarcoma viruses grown in hamster cells in vitro.

TUMOURS can be induced in hamsters by the various strains of murine sarcoma virus (MSV)1–6. Tumours differ, however, in the antigens which are expressed. Whereas the cell line HT-1, derived from early passages of a hamster tumour induced by the Moloney strain of MSV (M-MSV), contains no trace of infectious virus or virion antigen2,7, tumours induced by the Harvey (H), Kirsten (Ki) and later passages of the M-MSV-(GLV) viruses have yielded sarcoma viruses with a hamster-specific host range3–6,8 which do not share envelope4–6,9 or group specific10 antigens with murine viruses. The HT-1 cell does retain the MSV genome which can be rescued by murine leukaemia viruses2. Such rescued viruses are termed pseudo-types and contain the envelope and group-specific antigens of the rescuing virus. The virus preparation from tumours induced by M-MSV(GLV) differed from the other hamster-specific viruses in that a non-sarcomagenic C-type virus could be isolated from cultures infected beyond the cell transformation end point6. This virus was also hamster-specific in host range and antigenic properties and specifically interfered with cell transformation by the various hamster-specific virus strains9. This virus also shared an ether-stable virion-antigen with a C-type virus found in a lymphoma which occurred spontaneously in a hamster10. This shared antigen seems to be the principal structural polypeptide of hamster C-type viruses and is structurally similar but antigenically distinct from its mouse homologue (unpublished work of S. O., C. Foreman, G. K. and R. V. G.). These findings led us to propose that the hamster-specific non-sarcomagenic C-type virus was a hamster leukaemia virus (in the generic but not necessarily the pathological sense) and the virus is therefore designated HaLV9,10. The hamster-specific sarcoma viruses are considered to be pseudotypes of MSV rescued in vivo by HaLV and are abbreviated accordingly; for example, M-MSV(HaLV) represents the hamster-specific sarcoma virus rescued from M-MSV induced tumours. This is plausible because HaLV is able to rescue the MSV genome from HT-1 cells6. (This change in the nomenclature has been made in order to reflect the antigenic composition of the hamster-specific virus more accurately. In addition, to indicate the virus rescued from M-MSV(GLV)-induced hamster tumours, a terminal G is added after the parentheses. This has been done only to distinguish it from the virus obtained from M-MSV induced hamster tumours, for there is no evidence of residual activity from GLV.)