Congenital lymphocytic choriomeningitis virus infection

Daniel J Bonthius MD PhD (Dr. Bonthius of the University of Iowa has no relevant financial relationships to disclose.)
Bernard Maria MD, editor. (Dr. Maria of Icahn School of Medicine at Mount Sinai and Director of Pediatric Neurology and Developmental Medicine at Goryeb Children)
Originally released October 22, 2001; last updated October 24, 2016; expires October 24, 2019

This article includes discussion of congenital lymphocytic choriomeningitis virus infection, congenital LCMV infection, acquired LCMV infection, and postnatal LCMV infection. The foregoing terms may include synonyms, similar disorders, variations in usage, and abbreviations.

Overview

Lymphocytic choriomeningitis virus (LCMV) is a prevalent human pathogen that induces aseptic meningitis in children and adults. LCMV can also infect the fetus, where the virus targets the developing brain and induces substantial and permanent neuropathology. In this update, the author discusses the various forms of neuropathology that LCMV can induce and the critical role of patient age in determining the form and severity of pathology. He further discusses the differential diagnosis of congenital LCMV infection and the clinical and laboratory clues that help to distinguish congenital LCMV infection from other congenital infections.

Key points

 

• Lymphocytic choriomeningitis virus (LCMV) is endemic in wild mice throughout the world.

 

• Humans can become infected with LCMV through contact with the secretions or excretions of infected mice.

 

• In postnatal humans, LCMV typically produces a brief febrile illness that often includes aseptic meningitis.

 

• LCMV can cross the placenta, where it preferentially infects the human fetal brain and retina and causes substantial permanent injury.

 

• Much of the pathology induced by LCMV infection is immune-mediated.

Historical note and terminology

Lymphocytic choriomeningitis virus is a prevalent human pathogen and an important cause of neurologic birth defects in humans. Congenital LCMV infection is under-recognized by pediatricians and neurologists and is probably responsible for far more cases of congenital brain and retinal injury than has previously been realized (Enders et al 1999).

LCMV was first isolated in 1933 by Armstrong and Lillie from the cerebrospinal fluid of a woman who was thought to have St. Louis encephalitis. This patient had initially presented with general malaise, but her condition progressively worsened, and she died. The virus isolated from her cerebrospinal fluid was passaged 5 times through monkeys and, with each passage, produced a disease resembling St. Louis encephalitis. However, on the sixth passage, the virus was inoculated into a monkey that was immune to St. Louis encephalitis, yet still produced the disease. Armstrong and Lillie isolated this new infectious agent and named it lymphocytic choriomeningitis virus, for the pathologic changes that it induced in the choroid plexus and meninges of infected mice and monkeys (Armstrong and Lillie 1934).

The virus was subsequently isolated from cerebrospinal fluid of patients with aseptic meningitis, and it was soon firmly established that LCMV was an important etiologic agent of aseptic meningitis in man. Subsequent clinical and etiologic studies identified LCMV as one of the most frequent infectious causes of aseptic meningitis in humans (Meyer et al 1960). The first recognized case of congenital infection with LCMV was reported in England in 1955 (Komrower et al 1955). In the decades that followed, multiple cases of congenital LCMV infection were reported throughout Europe. Although LCMV has been recognized as an important cause of aseptic meningitis in the United States for decades, the first cases of congenital LCMV infection were not reported in this country until 1993 (Barton et al 1993; Larsen et al 1993).

Although LCMV was discovered in 1933, the virus was not classified until the late 1960s, when it was placed in the newly formed Arenaviridae family of viruses. The arenaviruses are enveloped single-stranded RNA viruses. The arena group of viruses gains their name from arenosus, the Latin word for "sandy," on the basis of the fine granularities observed within the virion on ultrathin electron microscopic sections (Buchmeier and Zajac 1999).

Like most arenaviruses, LCMV utilizes rodents as its principal reservoir. The only arenaviruses with nonrodent reservoirs are the Tacaribe virus, which infects bats, and an identified arenavirus found in boid snakes (Bodewes et al 2013).

Mus musculus, the common house mouse, is both the natural host and reservoir for LCMV, which is transferred vertically from one generation to the next within the mouse population by intrauterine infection. Hamsters are also competent reservoirs. Although they may be heavily infected with LCMV, rodents that acquire the virus transplacentally often remain asymptomatic because the virus is not cytolytic and because congenital infection in rodents provides them with immunological tolerance for the virus. Mice and hamsters infected with LCMV shed the virus in large quantities in nasal secretions, saliva, milk, semen, urine, and feces throughout their lives.

Postnatal humans typically acquire LCMV by direct contact with fomites contaminated with infectious virus or by inhalation of aerosolized virus. Postnatal humans can also acquire the virus via organ transplantation (Fischer et al 2006; Centers for Disease Control and Prevention 2008). Congenital LCMV infection occurs when a woman acquires LCMV during pregnancy. The virus is passed to the fetus transplacentally, presumably during maternal viremia. The virus may also be acquired by the fetus during the intrapartum period (Komrower et al 1955).

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