Immunofluorescence study of the carrier state and mechanism of vertical transmission in lymphocytic choriomeningitis virus infection in mice

Abstract

THE lymphocytic choriomeningitis (LCM) virus carrier state in mice was described by Traub in 1936. Mice, infected in utero or in early infancy, retain virus in their bodies for life, a state of affairs that Burnet and Fenner (1949) suggested was due to immunological tolerance to the virus. Vertical transmission, from mother to young, was demonstrated in carrier colonies, and the possibility of infection at an early stage of embryonic development was suggested by Traub (1960).The carrier state poses interesting problems in immunology, virology and pathogenesis, some of which have been admirably discussed by Hotchin (1962). A basic requirement for the solution of many of these questions is knowledge of the location and numbers of infected cells at various stages in the life of carrier mice, and the existence of the immunofluorescence method for such histological analysis of virus infections prompted this study. The recent paper by Wilsnack and Rowe (1964) is an important start in the understanding of the LCM infection at the histological level, and the studies on carrier mice made by these authors are confirmed and extended in the present report. MATERIALS AND METHODSMulticoloured outbred mice of the Walter and Eliza Hall Institute strain, which have been maintained in the University Animal Breeding Establishment since 1952, were used. The WE3 LCM virus carrier colony was originally established by the neonatal injection of mice by Lehmann-Grube (1964) and had been maintained for 2-3 yr (less than ten generations) at the time the experiments were carried out.Tissues were frozen in containers in liquid nitrogen and sections cut on a Cambridge Rocker microtome in a -20" refrigerator (Louis, 1957). Thoroughly dried sections were fixed in acetone for 10 min. at room temperature before staining.LCM-immune mouse serum, produced in carrier mice after transfusion with isologous mouse lymphoid cells (Volkert, Larsen and Pfau, 1964) was kindly supplied by Dr M. Volkert, Statens Serum Institut, Copenhagen. This serum had a complement-fixing (CF) antibody titre of 4096. Crude y-globulins were obtained by cold methanol precipitation and conjugated with fluorescein isothiocyanate (Sylvana Chemical Co., Orange, New Jersey) at a fluorescein/protein ratio of 1 /20. Mice.Fluorescent antibody technique.

Virus-triggered acquired immunodeficiency by cytotoxic T-cell-dependent destruction of antigen-presenting cells and lymph follicle structure.

“…2h) nude mice. The latter findings confirm that LCMV alone has no adverse effects on the integrity of lymphoid tissue (7). In addition spleens obtained from adult euthymic mice infected 4 days before analysis (Fig.…”

“…LCMV is non-or poorly cytopathic and replicates in many host cells (1)(2)(3)6); some LCMV isolates have tropism for lymphoid cells, particularly dendritic cells and macrophages (7)(8)(9); and LCMV may cause severe immune suppression in mice (8,(10)(11)(12)(13)(14)(15) and may establish persistent infections (1-3, [16][17][18].…”

“…Furthermore, in vivo treatment with anti-CD8 antibodies before or during infection was found to abrogate suppression (15). Both LCMV-WE and -DOCILE were shown to infect macrophages and dendritic cells but not CD8+ T cells or B cells during acute infection (7,8,21,22). In addition LCMV may infect a small percentage of CD4+ T cells; this is readily detectable in carriers but not in mice during the acute phase of the infection (23).…”

Studies on the susceptibility of the mouse preimplantation embryo to infection with cytomegalovirus

“…The viruses which cause murine leukaemia and mammary tumours in certain mouse strains are known to be transmitted vertically via the egg and early embryo (Zeilmaker, 1969;Bentvelzen, Daams, Hageman & Calafat, 1970;Gross, 1970). Similarly, it has been postulated that infection of the ovum and early embryo with lymphocytic choriomeningitis virus may be the route of transmission of this virus from parent to progeny (Mims, 1966). Experimental studies in vitro have shown that mouse preimplantation embryos are permissive hosts for the replication of several viruses and that embryonic infection usually causes abnormal development and embryonic death (Gwatkin & Auerbach, 1966;Sawicki, Baranska & Koprowski, 1971 ;Chase, Winters & Pikó, 1972;Biczysko, Solter, Pienkowski & Koprowski, 1973b;Mohanty & Bachmann, 1974).…”

Portraits of Viruses: Arenaviruses

“…Nor has the stage of development been de fined during which the developing embryo is susceptible. Ova in carrier mice may be in fected [Mims, 1966], but whether these have retained the ability to develop has not yet been determined. Being literally loaded with virus, it is not surprising that carrier mice do not develop symptoms when superinfected, a phenomenon called by Trauh [ 1939] 'infec tion immunity'.…”