Lymphocytic choriomeningitis virus — Questions

Infection of the fetal or newborn mouse, before the immune system matures, produces lifelong tolerant carriage with high virus levels but no disease.

This observation was central to the concept of immunological tolerance; the other outcomes do not describe it.

Acquired from an infected donor, LCMV causes a severe and frequently fatal multisystem illness in the immunosuppressed recipient, with fever, hepatitis, encephalopathy and multiorgan failure within weeks; across five US clusters most of the 17 recipients died.

Donors cannot practically be screened for this rare infection, so it is recognised after the event.

In the adult mouse the fatal disease is caused by the cytotoxic T-lymphocyte response, the classic demonstration that a virus-specific T-cell response can mediate immunopathology as well as viral clearance.

It is not due to direct neuronal lysis, antibody or complement, bacterial superinfection or immune-complex vasculitis.

Like the other Old World arenaviruses, LCMV binds alpha-dystroglycan to enter cells, followed by endocytosis and low-pH fusion.

Transferrin receptor 1 serves the New World arenaviruses and neuropilin-2 serves Lujo; CD4 and sialic acid are not its receptor.

LCMV was isolated in 1933 by Armstrong and Lillie during an investigation of a presumed St. Louis encephalitis outbreak, and was soon recognised as a distinct cause of aseptic meningitis.

The other conditions were not the setting of its discovery.

LCMV does not spread by ordinary contact; the only recognised human-to-human routes are across the placenta and through organ transplantation.

Respiratory, sexual, faecal-oral and vector transmission between people are not features of the virus.

LCMV meningitis characteristically produces a marked lymphocytic pleocytosis, sometimes over a thousand cells, with a low cerebrospinal fluid glucose.

The low glucose is a useful clue, since many viral meningitides leave it normal; the other patterns are not typical.

The natural reservoir of LCMV is the common house mouse (Mus musculus), which is infected for life and sheds virus in its excreta, giving the virus a worldwide distribution.

The other animals are reservoirs of unrelated agents.

After an incubation of about 1 to 2 weeks, symptomatic LCMV is often a biphasic illness: a febrile phase settles briefly and is then followed in a minority by aseptic meningitis.

The other courses are not characteristic of LCMV.

A history of maternal contact with wild or pet rodents in pregnancy should prompt consideration of congenital LCMV when the standard congenital-infection screen is negative in an infant with hydrocephalus and chorioretinitis.

The other exposures point elsewhere or are irrelevant.

LCMV is an Old World arenavirus, but unlike its relatives Lassa and Lujo it is not a haemorrhagic fever agent, and it is distributed worldwide rather than confined to Africa.

It is neither a New World virus nor a flavivirus, and it does not cause haemorrhagic fever.

LCMV is managed supportively, and although ribavirin has been used in severe and transplant-associated disease its benefit is not established.

There is no vaccine, aciclovir has no role, LCMV is generally handled at moderate rather than maximum containment, and the congenital injury is fixed by birth.

Using LCMV, Zinkernagel and Doherty showed that cytotoxic T cells recognise viral antigen only alongside self-MHC molecules, the principle of MHC restriction, for which they received the Nobel Prize.

The other concepts were established in different systems.