Product Code Database
An arenavirus is a bi- or trisegmented ambisense RNA virus that is a member of the family Arenaviridae. These viruses infect rodents and occasionally humans. A class of novel, highly divergent arenaviruses, properly known as reptarenaviruses, have also been discovered which infect snakes to produce inclusion body disease, mostly in boa constrictors. At least eight arenaviruses are known to cause human disease. The diseases derived from arenaviruses range in severity. Aseptic meningitis, a severe human disease that causes inflammation covering the brain and spinal cord, can arise from the lymphocytic choriomeningitis virus. Hemorrhagic fever syndromes, including Lassa fever, are derived from infections such as Guanarito virus, Junin virus, Lassa virus, Lujo virus, Machupo virus, Sabia virus, or Whitewater Arroyo virus. Because of the epidemiological association with rodents, some arenaviruses and are designated as .
The virus contains a beaded nucleocapsid with two single-stranded RNA segments. The nucleocapsid consists of a core of nucleic acid enclosed in a protein coat. Although they are categorized as negative-sense viruses, arenaviruses are ambisense. While sections of their genome encode genes in the negative sense (reverse polarity), other sections encode genes in the opposite (forward/positive sense) direction. This complex gene expression structure is theorized to be a primitive regulatory system, allowing the virus to control what proteins are synthesized at what point in the life cycle. The life cycle of the arenavirus is restricted to the cell cytoplasm.
The extreme termini of each RNA segment contains a 19 nucleotide highly conserved sequence that is critical for recruitment of the viral replication machinery and initiation of viral mRNA transcription and genomic DNA replication. The conserved 5' and 3' RNA termini sequences are complementary and allows each RNA segment to adopt a double-stranded RNA panhandle structure that maintains the termini in close proximity and results in a circular appearance to purified arenavirus genomic templates visualized by electron microscopy. The double-stranded RNA panhandle structure is critical for efficient viral RNA synthesis, but potential interterminal double-stranded RNA interactions must be transiently relieved in order to recruit the viral polymerase.
The S-segment RNA is approximately 3.5 kb, and encodes the viral nucleocapsid protein (NP) and glycoprotein (GPC). The L-segment RNA is approximately 7.2 kb, and encodes the viral RNA-dependent RNA-polymerase (L) and a small RING-domain containing protein (Z).
The Z protein forms homo oligomers and a structural component of the virions. The formation of these oligomers is an essential step for particle assembly and budding. Binding between Z and the viral envelope glycoprotein complex is required for virion infectivity. Z also interacts with the L and NP proteins. Polymerase activity appears to be modulated by the association between the L and Z proteins. Interaction between the Z and NP proteins is critical for genome packaging.
A third genus, Hartmanivirus (not to be confused with genus Haartmanvirus of vibrio bacteriophages in family Demerecviridae, order Caudovirales), has also been established, including other species that infect snakes. The organisation of the genome of this genus is typical of arenaviruses but their glycoproteins resemble those of . Species in this genus lack the matrix protein.
A fourth genus, Antennavirus, has also been established to accommodate two arenaviruses found in striated frogfish ( Antennarius striatus).Zhang YZ, Wu WC, Shi M, Holmes EC (2018) The diversity, evolution and origins of vertebrate RNA viruses. Curr Opin Virol 31:9-16 A third antennavirus has been detected in Chinook salmon and sockeye salmon.
Mammarenaviruses can be divided into two serogroups, which differ genetically and by geographical distribution:
When the virus is classified "Old World" this means it was found in the Eastern Hemisphere in places such as Europe, Asia, and Africa. When it is found in the Western Hemisphere, in places such as Argentina, Bolivia, Venezuela, Brazil, and the United States, it is classified "New World". Lymphocytic choriomeningitis (LCM) virus is the only mammarenavirus found worldwide because of its ubiquitous Old World host, the house mouse. Old and New World arenaviruses appear to have diverged ~45,000 years ago.
The Old World Mammarenaviruses originated ~23.1-1.88 thousand years ago, most likely in Southern Africa, while the New World Mammarenaviruses evolved in the Latin America-Caribbean region ~41.4-3.3 thousand years ago.
All of these diseases pose a great threat to public health in the regions where it is taking place. For example, when the Old World Lassa virus turns into Lassa fever, this usually results in a significant amount of mortality. Similarly the New World Junin virus causes Argentine hemorrhagic fever. This fever is a severe illness with hemorrhagic and neurological manifestations and a case fatality of fifteen to thirty percent. The way this virus spreads is through increased traveling to and from endemic regions. This traveling has led to the importation of Lassa fever into non-endemic metropolitan areas all over the world.
Arenavirus has also pinpointed as the cause of death of three donor organ recipients in Australia who contracted the virus after receiving kidney and a liver donations from a single infected organ donor in late 2006. All three died in the first week of 2007.
WHO and its Global Outbreak Alert and Response Network (GOARN) partners continue to support the Ministries of Health of the two countries in various facets of the outbreak investigation, including laboratory diagnosis, investigations, active case finding and follow-up of contacts.
Immunotherapy is another potential approach. Monoclonal antibodies against Junin virus have been tested in animal models. An immunotherapeutic agent active against all tested mammarenaviruses that use the transferrin receptor 1 as their receptor was under investigation in 2020.
Mammarenavirus
Old World complex
New World complex
Reptarenavirus
Hartmanivirus
Antennavirus
Evolution
The evolution of the Mammarenavirus genus has been studied. The New World and Old World species diverged less than 45,000 years ago. The New World species evolved between 41,400 and 3,300 years ago in the Latin America-Caribbean region. The Old World species evolved between 23,100 and 1,880 years ago, most likely in southern Africa.
Reservoirs
Some arenaviruses are zoonosis pathogens and are generally associated with rodent—transmitted disease in humans. Each virus usually is associated with a particular rodent host species in which it is maintained. Arenaviruses persist in nature by infecting rodents first and then transmitted into humans. Humans can be infected through mucosal exposure to aerosols, or by direct contact of abraded skin with the infectious material, derived from infected rodents. Aerosols are fine mists or sprays of rodent dried excreta, especially urine that is dropped in the environment. Most of the Arenaviruses caught by humans are within their own homes when these rodents seek shelter. The virus can be caught in factories, from food that has been contaminated, or within agricultural work areas. Humans' risk of contracting the Arenavirus infection is related to age, race, or sex within the degree of contact with the dried rodent excreta.
Epidemiology
Hosts
+ Arenavirus diseases and hosts
! Virus
! Disease
! Host
! Distribution Dandenong Dandenong hemorrhagic fever Unknown old world ( Australian cases from Serbia ) Lymphocytic choriomeningitis virus Lymphocytic choriomeningitis House mouse ( Mus musculus) Worldwide Lassa virus Lassa fever Natal Multimammate Mouse ( Mastomys natalensis) West Africa Junin virus Argentine hemorrhagic fever Drylands Vesper Mouse ( Calomys musculinus) Argentina Machupo virus Bolivian hemorrhagic fever Large Vesper Mouse ( Calomys callosus) Bolivia Guanarito virus Venezuelan hemorrhagic fever Short-tailed Cane Mouse ( Zygodontomys brevicauda) Venezuela Sabiá virus Brazilian hemorrhagic fever Unknown Brazil Tacaribe virus Bat ( Artibeus) Trinidad Flexal virus Influenza-like illness Rice rat ( Oryzomys) Brazil Whitewater Arroyo virus Hemorrhagic fever Woodrat ( Neotoma) Southwestern United States
Clinical diseases
Recent outbreaks
A new species of arenavirus named the Lujo virus has been linked to five patients who exhibited symptoms of viral hemorrhagic fever in South Africa. Scientists identify new lethal virus in Africa The disease originated near Lusaka, Zambia and spread to Johannesburg, South Africa, after the first patient was transported to a hospital there. The results of genetic sequencing tests conducted by epidemiologists at Columbia University in New York City, USA, and at the Special Pathogens Branch of the Centers for Disease Control in Atlanta, USA, provided evidence that the causative agent of the disease is a virus from the family Arenaviridae, which ultimately resulted in the deaths of four out of the five infected in Zambia and South Africa during the outbreak which began in September 2008.
Treatments
Very few treatment methods are available. The current lack of a licensed vaccine and limited therapeutic options for the arenavirus make it arguably among the most neglected virus groups. The only licensed drug for the treatment of human arenavirus infection is the nucleoside analogue ribavirin. Ribavirin reduces morbidity and mortality in humans infected with certain arenaviruses, such as LASV and JUNV infections, if it is taken in the early stages of the disease. Ribavirin displays mixed success in treating severe arenaviral disease and is associated with significant toxicities.
Experimental approaches
Effective antiviral drugs need to be produced at a low cost, taken orally, and able to withstand tropical climates due to the regions where these infections are occurring. For this reason high throughput screening (HTS) of small molecular libraries could be the answer to finding a better remedy. HTS collects libraries of small synthetic molecules that can be used to identify protein promoting "agonist" molecules or protein inhibiting "antagonist" interactions. With HTS sustainable antiviral drugs can be discovered against possible new human pathogenic viruses.
External links
|
|
