Mechanisms of persistence in arenavirus infections: a brief review.

A characteristic of the arenaviruses is persistent infections in their natural host. Age at infection is an important factor in the establishment of persistence. Infections early in life regularly result in persistence and this appears to be related to the immaturity of the immune system. Persistently infected animals make antibodies to the viral antigens, which indicates that the animals are not tolerant with respect to B cell functions. However, cytotoxic T cells cannot be demonstrated in persistently infected animals, suggesting a defect in effector T cell functions. The mechanisms leading to this defect in cytotoxic T cells have not been resolved. Persistence of arenaviruses in cell cultures is also regularly observed but the molecular basis for survival of the virus and cell in long-term cultures has yet to be clarified.

Role of natural killer cells in Pichinde virus infection of Syrian hamsters.

Pichinde virus produced a fatal infection in adult MHA hamsters but not LSH hamsters after intraperitoneal inoculation. After footpad inoculation, an 8-day swelling response was observed in LSH but not MHA hamsters; however, both strains survived infection by this route. Examination of the kinetics of viral replication in the two hamster strains inoculated by the two routes revealed a correlation between infectious centers and natural killer activity in cells obtained from spleens and popliteal lymph nodes. A subpopulation of cytolytic and infected cells which sedimented at about 3.0 to 4.5 mm/h in albumin gradients was found in greater numbers in MHA than in LSH hamsters. These data suggest that one factor contributing to the fatal outcome of Pichinde virus infection in MHA hamsters is the presence of excessive numbers of splenic target cells which possess properties of natural killer cells.

Susceptibility to fatal Pichinde virus infection in the Syrian hamster.

The data presented in this paper suggest that the susceptible MHA hamster strain possesses a spleen target cell for Pichinde virus replication which is minimally expressed in the resistant strain. This target cell co-purifies with cells mediating NK activity, raising the possibility that the NK cell itself may be the additional target cell for Pichinde virus replication in the susceptible hamster strain. We hypothesize that early virus replication in the spleens of IP-inoculated hamsters leads to an overwhelming proliferation of virus. In contrast, a footpad inoculation of Pichinde virus retards virus spread into the spleen, and the host's immune response can effectively clear the relatively low amount of virus. In addition, data have been presented that show that a footpad inoculation of Pichinde virus elicits swelling in resistant hamster strains at eight days after infection, but fails to evoke a response in the susceptible MHA hamster strain. The response is controlled by a single autosomal dominant gene, and suggests that the MHA hamster strain has a defective delayed-type hypersensitivity response. The gene responsible for footpad swelling appears to be distinct from the single autosomal dominant gene that controls virus replication in the popliteal lymph nodes of footpad-injected hamsters. The phenotype of survival, then, may be the result of either limited virus replication early in infection, or an effective anti-viral cell-mediated immune response, or both.

Abortive replication of vaccinia virus in activated rabbit macrophages.

During the course of infection of rabbits with vaccinia virus, macrophages obtained from the peritoneal cavity develop bactericidal activity and the replication of vaccinia virus becomes restricted in these cells. The abortive replication of vaccinia virus in the activated macrophages was characterized in the present study. The virus adsorbed to and was uncoated equally well in macrophages from both normal and infected rabbits. A burst of deoxyribonucleic acid synthesis of comparable magnitude took place 3 to 6 h after infection in both normal and activated macrophages. Although the production of viral antigens, as detected by immunodiffusion and immunofluorescence, was the same in both types of cells, very few virus particles were formed in activated as compared with normal macrophages. We conclude that a block in a late step of the virus replication cycle occurred in the activated macrophages.

Antigens of Pichinde virus I. Relationship of soluble antigens derived from infected BHK-21 cells to the structural components of the virion.

Antigens detected by the complement-fixation (CF) test were prepared from BHK-21 cells infected with Pichinde virus. The preparations contained two antigens demonstrable by immunodiffusion. The antigen present in abundance was heat stable, Pronase resistant, and had a molecular weight of 20,000 to 30,000 as estimated by gel filtration. Polyacrylamide gel electrophoresis of purified antigen demonstrated two low-molecular-weight polypeptides. An identical antigenic determinant was found by disrupting purified virus with Nonidet P-40; however, none of the viral polypeptides co-migrated with the polypeptides derived from purified CF antigen. Pronase digestion of disrupted virus did not alter antigenicity but degraded the viral peptides to sizes similar to those associated with the major CF antigen. These observations suggest that the major CF antigen of Pichnide virus is a cleavage product of the structural proteins of the virus.

Specific lysis of human colon tumor cells by antibodies to CEA and isoantigen A: dependence on rabbit serum or neuraminidase.

The 51Cr cytotoxicity test was used to measure specific antibody reactions against carcinoembryonic antigen (CEA) and isoantigen A on the surface of human colon tumor cells. When human serum or guinea pig serum was used as a source of complement, no anti-CEA or anti-isoantigen A cytotoxicity was demonstrable despite binding of specific antibodies and activation of complement at least through the C3 component on the cell surface. In contrast, specific anti-CEA and anti-isoantigen A cytotoxicity was demonstrated when rabbit serum was used as a source of complement. Specific antibody-mediated cell lysis was also achieved with guinea pig complement if the cells were treated with neuraminidase before testing. These results support the concept that certain tumor cells have surface properties that render them resistant to immune lysis.