Viral pathogenesis and resistance to defective interfering particles

Abstract

Recently presented evidence indicates that synthesis of defective interfering (DI) particles following infection of cultured cells with lymphocytic choriomeningitis (LCM) virus may result in self-curing¹. The genesis of DI particles can occur in cells infected with virtually any animal virus², and seems to be a host-controlled function³. Thus, these particles may represent a third line of defence—with the immune response and interferon—against virus invasion^3,4. LCM virus infection causes the rapid appearance of DI particles in tissue culture cells^5,6. Nevertheless, persistent infections can be easily established with LCM and other arenaviruses^7–9. The LCM-persistent infections are apparently maintained in these cultures by the genesis of DI-resistant viruses¹. This latter finding prompted us to determine whether such DI-resistant viruses occur in nature. Vertical transmission of LCM virus in the house mouse or neonatal infection of laboratory mice takes the form of a life-long inap-parent infection. These mice lack functional virus-specific T lymphocytes, but may make an antibody response against the invasion. It is known that LCM virus injected into a neonatal mouse can change during the course of the infection so that at least two different viral populations coexist in the same mouse¹⁰. DI particles are produced in abundance shortly after neonatal infection and this precedes the appearance of a virus population that, by plaque morphology, differs from the one originally inoculated¹¹. We report here the isolation of an LCM virus from persistently infected mice that is resistant not only to the DI particles which were produced shortly after neonatal infection with heterotypic virus but also to the DI particles that this virus itself induces in neonates. We know of no other report of viruses which can replicate normally in the presence of the DI particles they induce.