eMedicine Specialties > Infectious Diseases > Viral Infections

Arenaviruses

Author: Larry I Lutwick, MD, Professor of Medicine, State University of New York, Downstate Medical School; Director, Infectious Diseases, Veterans Affairs New York Harbor Health Care System, Brooklyn Campus
Contributor Information and Disclosures

Updated: May 15, 2009

Introduction

Background

Arenaviruses are ambistranded ribonucleic acid (RNA) viruses that cause chronic infections in rodents and zoonotically acquired disease in humans. In 1934, the prototypic Arenavirus, lymphocytic choriomeningitis (LCM) virus was first isolated during serial monkey passage of human material that was obtained from a fatal infection in the first documented epidemic of St. Louis encephalitis, a totally unrelated virus. LCM virus was the first recognized cause of aseptic meningitis in humans. Other arenaviruses from South America and Africa are classic causes of viral hemorrhagic fever syndrome. As was recently reported from California and as is observed in other emerging groups of viruses (eg, hantaviruses), newly recognized viruses and niches are observed periodically.¹

Arenaviruses have been divided into 2 groups based on whether the virus is found in the Old World (ie, Eastern Hemisphere) or the New World (ie, Western Hemisphere). LCM virus is the only Arenavirus to exist in both areas but is classified as an Old World virus. The following are the major viruses and the other recognized Arenaviridae listed in relationship to their rodent reservoirs.

Old World Arenaviruses

Lymphocytic choriomeningitis virus

Rodent -Mus musculus and Mus domesticus (ie, house mouse) and Mesocricetus auratus (ie, Syrian hamster)

Location - Europe, Asia, and the Americas

Habitat - Peridomestic, grasslands

Human contact - Primarily within households

Lassa virus^2,3,4

Rodent -Mastomys natalensis (ie, multimammate mouse)

Location - West Africa

Habitat - Savanna, forest clearing

Human contact - Primarily within houses

Mopeia virus

Rodent -M natalensis

Location - Southern Africa

Habitat - Savanna

Human contact - Unclear

Mobala virus

Rodent -Praomys species (ie, soft-furred rat)

Location - Central African Republic

Habitat - Savanna

Human contact - Unclear

Ippy virus

Rodent -Arvicanthus species (ie, Nile grass rat)

Location - Central African Republic

Habitat - Grassland, savanna

Human contact - Unclear

Classic New World Arenaviruses

Junin virus

Rodent -Calomys masculinus (ie, corn mouse), Akodon azarae (ie, grass field mouse), Bolomys obscurus (ie, dark field mouse)

Location - Argentina

Habitat - Grasslands, cultivated fields, and hedgerows

Human contact - Occupational in fields

Machupo virus

Rodent -Calomys callosus (ie, vesper mouse)

Location - Bolivia

Habitat - Peridomestic, grasslands

Human contact - Primarily within houses

Guanarito virus

Rodent -Sigmodon alstoni (ie, cane mouse)

Location - Venezuela

Habitat - Grasslands, brush

Human contact - Within houses

Sabia virus

Rodent - Unknown

Location - Isolated in Brazil

Human contact - Associated with several human cases, including a laboratory worker in Connecticut

Selected Less Common New World Arenaviruses

Tacaribe virus

Rodent -Artibeus species (ie, fruit-eating bat)

Location - Trinidad

Habitat - Tropical forest

Human contact - Unclear

Amapari virus

Rodent -Oryzomys goeldii (ie, rice rat), Neacomys guianae (ie, bristly mouse)

Location - Brazil

Habitat - Tropical forest

Human contact - Unclear

Tamiami virus

Rodent -Sigmodon hispidus (ie, hispid cotton rat)

Location - Florida

Habitat - Grasslands, marsh

Human contact - Unclear

Whitewater Arroyo

Rodent -Neotoma albigula (ie, white-throated wood rat)

Location - California, New Mexico

Habitat - Grasslands

Human contact - Unclear

Other viruses

Flexal virus (Brazil)

Pichinde virus (Columbia)

Latino virus (Bolivia, Brazil)

Parana virus (Paraguay)

Pathophysiology

Arenaviruses are lipid-enveloped, spherical-to-pleomorphic particles ranging in size from 50-300 nm. The envelope that surrounds the virion contains 2 major glycoprotein components (ie, GP1, GP2) that appear as spikelike or clublike projections with variable spacing along the virus lipid coat.

The Arenaviridae generally have been considered negative-sense RNA viruses that contain 2 subgenomic segments referred to as L (large) and S (small) of 2.4 million bases and 1.3 million bases, respectively. The 5' ends of both the L and S strands contain positive-sense RNA; therefore, the viruses are best considered ambisense. Each of the RNA segments consists of 2 nonoverlapped long open reading frames with opposite polarity. The L segment encodes for a Z protein and for the viral RNA-dependent RNA polymerase, and the S segment encodes for the glycoprotein precursors and for the N protein that binds to the positive-sense RNA segments.

A distinguishing characteristic of arenaviruses is the presence of internal granular structures 20-25 nm in size. On electron microscopy, these structures appear sandlike. The virus name (arena) is derived from the Latin root meaning sand. These components are thought to be host cell–derived ribosomes, which are incorporated into the virus during budding. The ribosomal structures are not believed to be essential in virus replication.

Frequency

United States

The number of cases of LCM virus infection is unclear, but a number of clusters have been reported related to pet hamsters or laboratory animals. Recently, 3 fatal cases of infection with a virus similar to Whitewater Arroyo virus were reported in California.

International

Scattered outbreaks of Lassa fever in western Africa and South American hemorrhagic fever occur, representing local public health problems. Public health officials in nonendemic areas must remain vigilant for these infections because imported cases have been described, presumably due to person-to-person spread.⁵

Mortality/Morbidity

Arenaviruses persist in nature by infecting rodents, primarily through a one-virus, one-rodent species relationship. Arenaviruses are transmitted to humans through aerosolization of dried excreta, especially urine that has been deposited in the environment.

• LCM virus: Infection occurs wherever either of the 2 closely related species of the common house mouse (M musculus, M domesticus) exists. The areas include Europe, the Americas, Australia, and Japan. Human infection is more common in rural areas, where a higher rate of infection exists in mice. Sporadic human LCM virus infections have autumn/winter predominance, when mice are more likely to seek human dwellings for shelter and food. Hamsters also can be infected and are more significant disease vectors in laboratory workers and pet owners.
• Lassa virus (ie, Lassa fever): Lassa fever is endemic to West Africa. Originally found in Nigeria, outbreaks have been reported from Sierra Leone, Liberia, and Guinea. Lassa virus was isolated from rodents of the genus Mastomys, members of which aggressively invade houses. Lassa fever is common in the dry season. This viral agent is noteworthy because of its ability to spread from person to person. This also occurs to some degree with South American viruses.^2,3,4
• South American viral hemorrhagic fevers 
  • These are diseases of South American countries, including Argentina, Bolivia, and Venezuela, caused by the viruses Junin, Machupo, and Guanarito, respectively.
  • For Argentine hemorrhagic fever, the main reservoir rodent is C masculinus. This rodent is found in the cornfields, especially from February through May. Therefore, men harvesting corn are particularly at risk. Infectious aerosols are thought to be the most common mode of transmission, but food contamination and direct contact of abraded fingers with blood or tissue from rodents may occur.
  • Bolivian hemorrhagic fever is found in the tropical savanna of the Beni region in northeastern Bolivia. The reservoir rodent is C callosus, which travels freely around this area. Bolivian hemorrhagic fever is commonly found from April to July. Transmission is believed to occur through aerosols from infected rodents or, possibly, through food contaminated by rodenturine.
  • Venezuelan hemorrhagic fever,causedby the Guanarito virus, has the cane mouse Zygodontomys brevicauda as a reservoir. People who have moved to the cleared forest areas for agricultural work are most at risk.

Age

The risk of human acquisition of Arenavirus infection is related to age, race, or sex only to the degree that these variables impact contact with dried rodent urine.

Clinical

History

A short synopsis of some of the historical and clinical points regarding the major Arenavirus illnesses is as follows:

• Lymphocytic choriomeningitis virus
  • This usually benign infection generally begins with fever, myalgia, and headache. Leukopenia and thrombocytopenia are revealed on laboratory studies.
  • The illness can be biphasic.
  • The second febrile period and some of the late complications (see Complications) may be immunologic in origin.
• Lassa fever
  • Most infections due to the Lassa virus are mild or subclinical.
  • Severe multisystem disease is believed to occur in 5-10% of total infections.
  • Incubation period is 7-18 days.
  • Illness begins insidiously with fever, weakness, malaise, joint and/or lumbar pain, cough, and severe headache.
  • In severe cases, illness progresses to include prostration, dehydration, abdominal pain, and facial or neck edema. Serum aminotransferases may be elevated. Note that Lassa fever stands alone among causes of viral hepatitis to have aspartate aminotransferase (AST) levels substantially higher than alanine aminotransferase (ALT) levels. This pattern has been classic for alcoholic hepatitis.
  • Lymphopenia, thrombocytopenia, and defects of qualitative platelet function are found during this stage.
• South American hemorrhagic fevers
  • Junin and Machupo viruses are similar in severity, and anecdotal reports suggest that Guanarito infections may be somewhat more severe overall.
  • The illnesses begin somewhat insidiously with fever, malaise, myalgia, and lumbar pain.
  • Progression may occur over 3-4 days, with prostration, unremitting fever, and mucosal bleeding. Hemorrhage along the gingival margins is characteristic.
  • After 1-2 weeks, most patients improve, but approximately one third progress to profound cutaneous and mucosal hemorrhages, delirium, and convulsions or a combination of CNS and bleeding findings. Capillary leak syndrome also may occur.

Physical

The major physical points regarding the major Arenavirus illnesses are as follows:

• Lymphocytic choriomeningitis virus
  • Conjunctival injection, facial flushing, generalized lymphadenopathy, and orthostatic hypotension are common.
  • Fever and more severe headaches may recur 2-4 days after recovery from the first phase, with overt lymphocytic pleocytotic meningitis with elevated cerebrospinal (CSF) protein. Papilledema may be noted.
• Lassa fever
  • Pharyngitis, often exudative, occurs early. Conjunctivitis also may be seen.
  • Later, in severe disease, CNS signs can be seen, including tremors, confusion, encephalopathy, and seizures. Focal CNS signs usually are absent, and CSF is normal.
  • Bleeding is seen in only 15-20% of patients, it usually is limited to mucosal surfaces, and it is limited in severity.
• South American hemorrhagic fever
  • Conjunctival injection, facial flushing, generalized lymphadenopathy, and orthostatic hypotension are common signs.
  • Many patients have a petechial and/or vesicular palatal enanthem and skin petechiae.
  • At the point of further progression, CNS signs can include tremor of hands and tongue, hyperesthesias, decreased deep-tendon reflexes, and lethargy.
  • Especially with deteriorating illness, leukopenia and thrombocytopenia are common but aminotransferase elevations are uncommon.

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