Virus-specific neutralization by a soluble non-immunoglobulin factor found naturally in normal mouse sera.

Abstract

A low-molecular-weight substance found naturally in mouse serum neutralizes mouse xenotropic Ctype virus. It has no effect on endogenous ecotropic viruses. This neutralizing factor does not belong to the known immunoglobulin classes, and its activity is not associated with the antivirus immunoglobulins that can be detected by radioimmunoprecipitation. Preparations of xenotropic virus absorb out this neutralizing activity in mouse sera. The specificity of this factor for X-tropic virus suggests that it represents a newly recognized type of response of the host to an endogenous virus. Its possible role in the regulation of endogenous C-type viruses is considered.The genomes of murine C-type RNA viruses (MuLV) are integrated as DNA copies in the chromosome of the mouse and can be passed by the germ cell to successive generations (i.e., endogenous virus) (1-4). Production of these endogenous viruses by mouse cells may occur spontaneously or after activation by a variety of experimental means (5-8). Two classes of MuLV that are based on host range have been described in laboratory and certain wild strains of house mice: ecotropic and xenotropic (9-11). The ecotropic viruses, exemplified by the AKR isolates (12), have been recovered from many, but not all, strains of mice; they productively infect mouse cells and can give rise to malignancy in the mouse (2, 10-12). The xenotropic viruses (X-tropic), originally described in New Zealand Black (NZB) mice (13), are probably present in all strains of the Mus musculus species (8-11, 13-15); they have an envelope coat antigen distinct from ecotropic viruses (9-11). Although produced endogenously by mouse cells, these X-tropic viruses cannot productively infect mouse cells, but are infectious for a wide variety of heterologous mammalian and avian cells (16). The role of X-tropic viruses in any pathologic process in the mouse is unknown. Radioimmunoprecipitation (RIP) techniques have indi-cated the natural occurrence of immunoglobulins of the IgM and IgG classes in most mouse sera; these immunoglobulins will bind to both ecotropic and xenotropic viruses (17, 18). However, these same mouse sera neutralize only xenotropic viruses, not ecotropic viruses (10,11,(19)(20). In general, the titer of neutralizing activity against X-tropic viruses varies between 1:100 and 1:400, but titers may reach levels as high as 1:10,000 (11, 21). Titers of antiviral immunoglobulins, as determined by RIP, range between 10 and 5000, depending on the mouse strain (22). It was assumed that the mouse immunoglobulins (Ig) whose binding to virus could be detected by RIP were responsible for the neutralization of X-tropic virus. The specificity of neutralization, however, could not be explained, inasmuch as these mouse Ig bind equally to both classes of MuLV

A new class of murine leukemia virus associated with development of spontaneous lymphomas.

“…247 virus both before and after limiting-dilution purification. Like xenotropic MuLV strains (11,12), the mink cell focusinducing (MCF) viruses are neutralized by normal NZB mouse serum (Table 1).…”

Genetic Control of a Mouse Serum Lipoprotein Factor That Inactivates Murine Leukemia Viruses: Evaluation of Apolipoprotein F as a Candidate

“…This strain difference was used in a classical genetic analysis to determine that a single gene controls the presence of this factor. This factor is likely to be the same serum factor described in earlier studies (7,14) because of its specificity for xenotropic and polytropic MLVs, its absence in some NIH Swiss-derived strains, and its insensitivity to heat inactivation.…”

“…This factor, here termed leukemia virus-inactivating factor (LVIF), was found to be stable when exposed to acid pH, ether extraction, freezing, proteases, and brief boiling (12). This factor is separable from immunoglobulin (7,14) and is also distinct from complement, indicating that it has no relationship to the complementmediated lysis of oncornaviruses by human sera (3).…”

“…For example, 25 years ago, several laboratories (7,14) determined that mouse serum contains a factor that inactivates the xenotropic subgroup of the MLVs. This factor, here termed leukemia virus-inactivating factor (LVIF), was found to be stable when exposed to acid pH, ether extraction, freezing, proteases, and brief boiling (12).…”

Biological Characteristics of Type C Viruses Isolated from Different Friend Erythroleukaemic Cells

“…These tests were performed as described by Levy et al (1975) with anti-xenotropic virus sera, prepared against NZB xenotropic virus, and anti-FMR (anti-ecotropic) sera obtained from J. Levy, who performed some of these studies for us.…”