Chapter: Microbiology and Immunology: Virology, Virus: Miscellaneous Viruses

Arenavirus

Arenaviruses are enveloped viruses with a helical nucleocapsid. They are spherical to pleomorphic in shape varying in size from 50 to 300 nm.

Arenavirus

Arenaviruses are enveloped viruses with a helical nucleocapsid. They are spherical to pleomorphic in shape varying in size from 50 to 300 nm. The lipid envelope contains two major glycopro-tein components gp1 and gp2, which appear as spike-like or club-like projections. The name arena means sand that refers to granules at the surface of the virion that are nonfunctional ribosomes. The arenaviruses include lymphocytic choriomen-ingitis (LCM) and hemorrhagic fever viruses, such as the Lassa, Junin, and Machupo virus.

Properties of the Virus

 Morphology

Arenaviruses show following features:

·           Arenaviruses are the pleomorphic, enveloped viruses (50–300 nm) that have a sandy appearance.

·       The genome is a negative-sense RNA that contains two subgenomic segments, namely, S (small segment, measuring 1.3 million        bases)         and L (large segment, measuring  2.4 million bases).

·           The virion consists of beaded nucleocapsid with two single-stranded RNA circles. The strand is a negative-sense RNA that encodes for a Z protein and for the viral RNA-dependent RNA polymerase.

·           The segment encodes for the glycoprotein precursors and for the N protein that binds to the positive-sense RNA segments. The presence of internal granular structures 20–25 nm in size is the distinctive property of arenavirus. These granular structures on electron microscopy appear sand-like. These structures are believed to be host-cell-derived ribosomes, which are incorporated into the virus during budding. These struc-tures do not appear to play any role in replication of viruses.

Viral Isolation

The arenavirus, such as Lassa virus, can be isolated in cell culture using the E6 clone of Vero cells or in suckling mice.

Pathogenesis and Immunity

Arenaviruses primarily infect macrophages and cause the vas-cular damage. Pathogenesis of arenaviruses infection is largely attributed to T-cell immunopathogenesis. T-cell-induced immunopathogenic effect contributes to the exacerbation of tissue destruction.

Clinical Syndromes

Arenaviruses cause the following diseases: Lymphocytic chorio-meningitis, Lassa fever, and South American hemorrhagic fever.

 Lymphocytic choriomeningitis

Lymphocytic choriomeningitis virus causes lymphocytic cho-riomeningitis. This is a benign infection, which usually begins with fever, myalgia, and headache. The illness can be biphasic. Fever and more severe headache may recur 2–4 days after recov-ery from the first phase.

 Lassa fever

Most infections caused by Lassa fever virus are mild or subclini-cal. The incubation period varies from 7 to 18 days. The infec-tion begins insidiously with fever, malaise, joint pain, cough, and severe headache. Prostration, dehydration, abdominal pain, facial or neck edema may be seen in severe cases.

 South American hemorrhagic fever

Lassa, Junin, and Machupo viruses cause South American hemorrhagic fever, which are similar in severity. This has an insidious onset with fever, malaise, myalgia, and lumbar pain. A petechial and/or vesicular palatal enanthem and skin pete-chiae are found in many patients. The condition may prog-ress within 3–4 days with prostration and remitting fever and mucosal bleeding. Gingival hemorrhage is the characteristic feature. Most patients improve after 1–2 weeks, but one-third of patients may show many complications. These complica-tions include profound mucocutaneous and mucosal hemor-rhages, delirium, and convulsions.

Epidemiology

 Geographical distribution

Most arenaviruses with exception of lymphocytic chorio-meningitis viruses are found in Africa and South America.

 Reservoir, source, and transmission of infection

Most of arenaviruses are zoonotic and disease is transmitted primarily from rodents to humans. These viruses cause infec-tion in specific rodent species and are endemic in the areas that are inhabited by rodent species. The viruses that cause chronic infection in these animals are excreted in saliva, urine, and feces over a very long period of time. Humans usually acquire infec-tion from these animals through:

·           inhalation of infectious aerosols of dried excreta, especially urine of the rodents that has been passed in the soil.

·           ingestion of food contaminated with rodent feces or urine, or

·           contact of the abraded skin with rodent blood or serum. The infections are not usually transmitted by the bite of rodents.

The LCM viruses are distributed in Europe, Australia, Japan, and the Americas. This infection in this area is closely related with presence of infection in common mouse, such as Musmusculus and Mus homisticus. The mice are the most importantreservoir of infection for humans. Hamsters are important res-ervoirs for pet owners and laboratory workers.

Lassa fever is the disease of West Africa. The outbreaks of Lassa fever have been reported from Nigeria, Sierra Leone, Liberia, and Guinea. The rodents of the genus Mastomys are the reservoirs of infection. The infection is transmitted from these infected mice to humans. The infection can also be transmitted from humans to humans.

South American hemorrhagic fever is caused by viruses Junin, Machupo, and Guanarito, which are endemic in Argentina, Bolivia, and Venezuela, respectively. The rodent Calomys mus-culinus is the main reservoir for Argentine hemorrhagic fever.These rodents, which are found commonly in the corn field, transmit the virus to farmers harvesting the corn. The infection is transmitted by inhalation of infectious aerosols. The infec-tion can also be transmitted by ingestion of contaminated food and also by direct contact of blood or tissue from rodents on the abraded finger.

The rodent Calomys callosus is the major reservoir for Bolivian hemorrhagic fever, which transmits infection to humans. Transmission of infection occurs through these rodents by inhalation of aerosols from infected organisms and also by ingestion of food contaminated by rodent urine. The cane mouse is the main reservoir for Venezuelan hemorrhagic fever.

Laboratory Diagnosis

There is a great risk for laboratory workers in handling body fluids for diagnosis. Hence, it is mandatory to process the spec-imen only in facilities with biosafety level 4 for Lassa fever and other arenaviruses and biosafety level 3 for LCM virus.

 Specimens

The specimens include blood and CSF.

 Isolation of the virus

The virus can be isolated easily from blood of the individuals suffering from LCM virus infection and also from the CSF of the individuals developing meningitis. South American hemorrhagic fever viruses can be isolated from blood or tissue using tissue culture or suckling mice. Lassa virus can be cultured in tissue culture using the E6 clone of Vero cells or in suckling mice.

 Serodiagnosis

Serodiagnosis is the most important method for establishing the diagnosis of arenavirus infection in humans.

Treatment

Ribavirin is the antiviral drug used for the treatment of Lassa fever and also for South American hemorrhagic fever. The treatment is mostly supportive to maintain fluid and electro-lyte balance, which can be lifesaving.

Prevention and Control

The prevention of rodent-borne arenavirus infection depends on the rodent control measures and avoidance of high-density rodent-infested areas. No vaccines are available against arenaviruses. Clinical trials of attenuated Junin virus are in progress.


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