Conversion of Genetic Resistance of Mammalian Cells to Susceptibility to a Virus Infection

Kańtoch, M; Bang, Frederik B.

doi:10.1073/pnas.48.9.1553

Cited by 19 publications

(7 citation statements)

References 3 publications

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“…Genetic Aspects of Macrophage Susceptibility.--It was first necessary to see whether peritoneal macrophages from susceptible mice were susceptible. As has been briefly reported (5) we found the macrophages of the PRI strain of mice fully susceptible and those of the C3H resistant. (Figs.…”

Section: Resultssupporting

confidence: 75%

The Cellular Nature of Genetic Susceptibility to a Virus

Kańtoch

Warwick

Bang

1963

The Journal of Experimental Medicine

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PLATES 45 ~o 50(Received for publication, January 9, 1963) It is now well established that a number of animal virus diseases (1) as well as plant diseases (2) are directly affected by the genetic makeup of the host. In some cases resistance is dominant; in at least one (mouse hepatitis) susceptibility seems dominant (3). The demonstration that the macrophage is the cell which is paramount in susceptibility to mouse hepatitis virus, MItV, (4) was followed by a demonstration that cultures of newborn mouse liver from susceptible mice yielded susceptible macrophages and from resistant mice yielded resistant cells (3). The susceptibility factor was manifested in the hybrids, F~, and back-cross generations of cultures from young mice as well as in whole mice. It was, therefore, inferred that genetic susceptibility resides in the cells--in particular in the macrophages. In order to test this definitively, four kinds of tests have been carried out directly in the mice and in their cells, and the four methods compared: (a) individual mouse susceptibility (phenotype), (b) production of susceptible offspring (genotype), (c) susceptibility of macrophages from liver cultures, and (d) susceptibility of macrophages from peritoneal washings of adult mice. The first part of this paper reports the results of these correlations, describes the susceptibility of several back-crosses, and confirms the cellular nature of genetic susceptibility to this virus. The second part deals with the susceptibility of peritoneal macrophages in culture and the conversion of resistant to susceptible cells by the addition of extracts of the susceptible cells to cultures of resistant cells (5). If there is a correlation between the susceptibility of macrophages and the susceptibility'of the individual animal to MHV infection, then different kinds of cross and back-cross generations of susceptible and resistant animals can be studied by examining their macrophages without sacrificing the mouse, and the progeny can be used for selective breeding.

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Section: Resultssupporting

confidence: 75%

The Cellular Nature of Genetic Susceptibility to a Virus

Kańtoch

Warwick

Bang

1963

The Journal of Experimental Medicine

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“…The original work indicating that resistant C3H cells could be made susceptible when treated with an extract of susceptible PRI cells was aimed at testing the question whether susceptibility could be directly transferred (7,8). The MLC experiments, on the other hand, suggested that the susceptibility of the macrophages was altered by a factor unrelated to susceptibility per se.…”

Section: Resultsmentioning

confidence: 99%

“…In addition, we now have been able to introduce the gene for susceptibility from the PRI mice into the C3H mice by the appropriate crosses and backcrosses and have established congenic lines of C3H, i.e., C3Hss (susceptible) and C3H (resistant), or in genetic terms, C3Hrr. It was the establishment of these two lines of mice which allowed us to differentiate between a hypothesis of conversion, presumed to be like that of transformation (7), and a change in susceptibility brought about by a mixed lymphocyte reaction. In 1962 when the original work on conversion was reported, there was little knowledge of lymphokines and their effect on macrophages.…”

Section: Discussionmentioning

confidence: 99%

Macrophages genetically resistant to mouse hepatitis virus converted in vitro to susceptible macrophages.

Weiser¹,

Bang²

1976

The Journal of Experimental Medicine

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Genetically resistant C3H mice have been made phenotypically susceptible to mouse hepatitis virus (MHV) by cortisone (1), cytoxan (2), and eperythrozoon infection (3). Materials and MethodsMice. Three inbred strains of mice were used: PRI, a genetically susceptible strain (4); C3H, a genetically resistant strain (4); and C3Hss, a strain that carries a single gene for susceptibility. Both the PRI and C3H strains have been maintained in our laboratory through brother-sister mating since 1955 (4). The C3Hss was developed in this laboratory by backcrosses with PRI mice; progeny were selected on the basis of susceptibility of their cultured macrophagee to destruction by the Princeton strain of MHV (MHV.PRI). Mice from two other strains that are not histocompatible with the C3H strain were also used. These were C57 black/6 and DBA/2 stock mice, 4-6-wk old, from The Jackson Laboratory, Bar Harbor, Maine. Virus. The MHV-2 strain of mouse hepatitis virus was originally obtained from Dr. JohnNelson of the Rockefeller Institute, Princeton, in 1952, and has since been passed in our laboratory by intraperitoneal inoculation of l-too-old PRI mice. This is the the MHV-PRI virus. A 10% (wt/ vol) liver homogenate was prepared by grinding up livers of moribund infected mice in Hanks' balanced salt solution (BSS) (Grand Island Biological Co., Grand Island, N. Y.). This was kept as stock virus and stored at -70°C.Macrophage Cultures. Methods of harvesting and preparing cultures of mouse peritoneal macrophages have been previously described (5). In the present experiments, macrophages were seeded in 13 x 100-ram Wassermann tubes and incubated at 37°C in a roller drum.MLC. Individual spleens from PRI, C3H, and C3Hss mice were removed and passed through a 60-mesh stainless steel wire cloth (Small Parts, Inc.). Cells were counted and suspended in a medium consisting of 80% RPMI-1640 (Grand Island Biological Co.), 20% Chang's medium (6) (90% horse serum, 8% Hanks' BSS and 2% beef embryo extract), and 100 U/rag per ml of penicillin and streptomycin. Equal amounts of PRI and C3Hss or C3H lymphocytes were mixed and cultivated in glass Petri dishes in a 37°C incubator maintained with 5% CO2. C57 black/6 and DBA/2 spleens were processed and cultivated in the same manner.

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“…Further backcrosses showed that the PRI gene for macrophage susceptibility was constant and completely manifest even when present in a C3H (resistant) background: the plaquing efficiency of the virus in macrophage cultures from susceptible mice of the BC7 generation was as high as that in PRI cultures (134); macrophage cultures continued to segregate in ratios close to 1:1 during 20 backcross matings; and macrophages obtained from the virus-susceptible inbred line of C3HSS mice, which are congenic with resistant C3H mice and only differ from these at the locus for MHV susceptibility, were just as susceptible as macrophages from the PRI mice, from which the gene for susceptibility was transferred (160). The expression of the genotype for susceptibility or resistance was not confined to liver macrophages, since the same picture emerged when macrophages were cultured from other tissues (13) or from peritoneal exudates (70,71).…”

Section: Ssmentioning

confidence: 92%