Lymphocytic Choriomeningitis Virus (LCMV) Infection

Updated: Mar 02, 2023
  • Author: Lea M Monday, MD, PharmD; Chief Editor: Michael Stuart Bronze, MD  more...
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Lymphocytic choriomeningitis virus (LCMV) is an enveloped single-stranded RNA virus first isolated in the cerebrospinal fluid of a woman during the 1933 Saint Louis encephalitis epidemic. [1]

LCMV belongs to the viral family Arenaviridae and was the first one discovered. Members of the Arenaviridae family are divided based on geographic distribution and genetic similarities as either Old World (Eastern hemisphere) or New World (Western hemisphere) arenavirdiae. Old world viruses include the Lassa virus (LASV) and Lujo fever in Africa, while New World viruses include several viral hemorrhagic fevers (Junin, Machupo, Guanarito, Sabia, Chapare) found in South America. [2, 3]  LCMV has potential for worldwide distribution; however, human cases have been documented only in the Americans and Europe, thus it is the only Old World arenavirus found in both the Eastern and Western Hemisphere. [3, 4]  

Arenaviruses are transmitted by rodents. Often 1 or a few rodent species serves as the natural reservoir for a given virus. [3]  There are 3 possible outcomes for an infected rodent: rapid clearance of virus, development of an acute lethal disease, and persistent chronic infection which is clinically benign but results in the release of virus into excreta, specifically urine. [2, 5, 6]  These infected but asymptomatic (carrier state) rodents, most commonly mice (Mus domesticus, Mus musculus), hamsters, and Guinea pigs, may serve as reservoirs for LCMV to be spread to humans. [5, 6]  Both vertical transmission to rodent offspring and horizontal spread contribute to the maintenance of virus in the rodent population.

LCMV is most commonly transmitted from mice to humans via inhalation of infected excreta (urine, droppings, saliva, or other nesting materials) which can be aerosolized during sweeping or cleaning. Direct contact with excreta and animal bites are another potential route of LCMV infection in pet handlers, rural workers, or laboratory technicians. [6, 7]  Other methods of human transmission include solid organ transplant and perinatal infection from mother to fetus. [2, 3, 4, 8, 9, 10, 11, 12]



The initial viremia of LCMV infection (phase 1) extensively seeds extra-CNS tissue. The secondary viremia (phase 2) infects the meninges and, less commonly, the cortical tissue. The leptomeninges are infiltrated mainly by lymphocytes and histiocytes, with few neutrophils. In LCMV encephalitis, the same type of inflammatory cells is observed in the perivascular Virchow-Robin spaces. LCMV is not cytotoxic. It appears that the host's immune response to the infected cells produces the various manifestations of this disease. Natural killer (NK) cells are first to respond, followed by the production of interferon by cytotoxic T cells. LCMV antibodies become detectable during the second febrile episode. In addition, LCMV can suppress the production of acetylcholine neuronal cells in cell culture. [2, 13, 14, 3, 15]

LCMV may affect the autonomic nervous system, various sensory modalities, and cranial nerves. Rarely, the virus can cause long-term neurologic sequelae, including chronic headache, hydrocephalus, deafness, transverse myelitis, and Guillain-Barré syndrome. [16] Other organs, especially the testes, heart, and joints, may be involved. Orchitis usually is unilateral and develops 1-3 weeks after illness onset. Cardiac involvement can occur in the form of viral myocarditis or pericarditis. The metacarpophalangeal joint and the proximal interphalangeal joint are the most common sites of arthritis caused by LCMV. The objective swelling, redness, and pain resolve within a few weeks. [14, 3, 17]

Pathopysiology in Special Populations:

Vertical transmission of LCMV during pregnancy has been associated with increased risk for spontaneous abortion and severe birth defects which can result in fetal death. [2, 18, 19] It also can cause a syndrome of hydrocephalus, chorioretinitis, and perivascular calcifications similar to that seen in congenital cytomegalovirus (CMV) infection and toxoplasmosis, potentially leading to mental retardation, microcephaly, seizures, and blindness. [18]

In solid organ transplant recipients with donor-derived infection (DDI), LCMV has been shown to cause severe illness characterized by multisystem organ failure. [8]  Four clusters of donor-derived LCMV infection have been described in the United States involving between 2003 and 2011, and an additional cluster was reported in Australia in 2008. [9, 10, 20, 11, 12]  The first US clusters occured in 2003 (4 recipients) and 2005 (4 recipients), and 7 of 8 died. Recent acquistion of a pet hamster with LCMV proven in the 2005 cluster. [20, 9]  A third US cluster occured in 2008 in 2 renal transplant recipients, 1 of whom died. [11]  A fourth US cluster occured in 4 patients in 2011, with death occuring in 2 patients. [10]  Meningitis is a less-prominent feature in these individuals and pathology at autotopsy has shown hepatocellular necrosis even in patients who did not receive a liver transplant. [10, 20]  In total, only 14 US organ recipients have acquired LCMV from an organ donor, 11 of whom died. The high degree of morbidity and mortality can be attributed to profoundly decreased cell-medicated immunity due to immunosuppression.




United States

Underreporting and a lack of routine testing for LCMV infection in most patients presenting with an acute viral illness limit ability to estimate incidence rates and prevalence of disease among humans. A human seroprevalence study from the 1990s detected antibodies to LCMV in 4.7% of 1180 patients living in urban Baltimore, while LMCV antibody was detected in 9% of the house mice living in the same area. [21, 6]  Other seroprevelance studies of patients in Texas and Alabama showed seropositivity for LCMV in the range of 2-5% [22]  

The incidence of LCMV is unknown. In a 2011 study of 1,185 patients from across the United States with acute central nervous system disease or undifferentiated febrile illnesses, antibody to LCMV was positive in 29 (2.4%) patients, though it is unclear in which it may have explained the illness in question. [23]  The true incidence of LCMV infection is suspected to be higher because of underreporting and missed diagnoses, with some sources citing 10% or more cases of aseptic meningitis may be due to LCMV. [24] LCMV infection in humans is most common in autumn due to migration of mice into warm structures prior to winter. [3]


Seropositvity of LCMV exposure has been studies in other countries outside of the United States, and LCMV infections have been reported in North America, South America, Europe, Australia, and Japan. [3, 25, 26]


LCMV infection has no racial predilection.


LCMV infection has no sexual predilection.


LCMV infection is more common in young adults, although illness may occur in any age group. [3]




Mortality and morbidity can result from the following:

  • Post Natal infection : The true mortality and morbidity for LCMV in adults and children is difficult to discern since the exact incidence is unknown. Estimates put the overall mortality rate of less than 1%, however, immunosuppressed patients are more prone to the complications of encephalitis or multisystem organ failure including hemorrhage, which may result in death. [24]
  • Congenital infection : The prognosis for infants with congenital LCMV infection generally is poor. A 1997 case series of congenital LCMV infection found a mortality rate of 35% by 21 months of age and severe neurodevelopmental disorders in those that survived. [19]  A more recent 2022 series of 70 reported cases of congenital LCMV infection found major cerebral abnormalities in 70% (49/70), a high mortality rate (30%), and severe neurologic sequelae reported in survivors. [18]
  • Infection acquired via Solid-Organ Transplant : Four clusters of LCMV acquired from donor to recipients via solid-organ transplant have been described in the United States. [9, 10, 20, 11]  Prognosis in donor-derived diseases is poor, with death reported in 11 of 14 transplant recipients (79%).