Arenavirus

File:Viruses-12-00784-g001.png

Viewed in cross-section, arenaviruses contain grainy particles that are ribosomes acquired from their host cells. It is from this characteristic that they acquired the name arena, from the Latin root meaning sand.{{cite journal |last1=Rowe |first1=Wallace P. |last2=Murphy |first2=Frederick A.|last3=Bergold |first3=Gernot H. |last4=Casals |first4=Jordi |last5=Hotchin |first5=John |last6=Johnson |first6=Karl M. |last7=Lehmann-Grube |first7=Fritz |last8=Mims |first8=Cedric A. |last9=Traub |first9=Eric |last10=Webb |first10=Patricia A. |title=Arenoviruses: Proposed Name for a Newly Defined Virus Group |journal=Journal of Virology |date=May 1970 |volume=5 |issue=5 |pages=652 |doi=10.1128/jvi.5.5.651-652.1970 |pmid=4986852|pmc=376052 }} The ribosomal structures are not believed to be essential for virus replication. Virus particles, or virions, are pleomorphic (variable in shape) but are often spherical, with a diameter of 60–300 nm, and are covered with surface glycoprotein spikes.{{cite journal | doi = 10.1016/j.virol.2011.01.013 | title = Arenavirus reverse genetics: New approaches for the investigation of arenavirus biology and development of antiviral strategies | year = 2011 | last1 = Emonet | first1 = Sebastien E. | last2 = Urata | first2 = Shuzo | last3 = De La Torre | first3 = Juan C. | journal = Virology | volume = 411 | issue = 2 | pages = 416–425 | pmid = 21324503 | pmc = 3057228 }}

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,{{Cite web|url=https://talk.ictvonline.org/ictv-reports/ictv_9th_report/negative-sense-rna-viruses-2011/w/negrna_viruses/203/arenaviridae|archive-url=https://web.archive.org/web/20181219043923/https://talk.ictvonline.org/ictv-reports/ictv_9th_report/negative-sense-rna-viruses-2011/w/negrna_viruses/203/arenaviridae|archive-date=19 December 2018|title=Arenaviridae - Negative Sense RNA Viruses - Negative Sense RNA Viruses (2011)|website=International Committee on Taxonomy of Viruses (ICTV)|language=en|access-date=2019-05-23}} 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.{{cn|date=October 2022}}

File:Genomes of Arenaviridae.png

Arenaviruses have a segmented RNA genome that consists of two single-stranded ambisense RNAs.{{cite journal|vauthors=Añón MC, Grau O, Segovia ZM, Franzefernández MT|date=June 1976|title=RNA composition of Junin virus|journal=J. Virol.|volume=18|issue=3|pages=833–8|doi=10.1128/JVI.18.3.833-838.1976|pmc=354781|pmid=178925}} As with all negative-sense RNA viruses, the genomic RNA alone is not infectious and the viral replication machinery is required to initiate infection within a host cell.{{cite journal|vauthors=Lee KJ, Novella IS, Teng MN, Oldstone MB, de La Torre JC|date=April 2000|title=NP and L proteins of lymphocytic choriomeningitis virus (LCMV) are sufficient for efficient transcription and replication of LCMV genomic RNA analogs|journal=J. Virol.|volume=74|issue=8|pages=3470–7|doi=10.1128/jvi.74.8.3470-3477.2000|pmc=111854|pmid=10729120}} Genomic sense RNA packaged into the arenavirus virion is designated negative-sense RNA, and must first be copied into a positive-sense mRNA in order to produce viral protein.{{cite conference|vauthors=Meyer BJ, de la Torre JC, Southern PJ|title=Arenaviruses: Genomic RNAs, Transcription, and Replication |year=2002|book-title=Arenaviruses I|series=Current Topics in Microbiology and Immunology|volume=262|pages=139–57|doi=10.1007/978-3-642-56029-3_6|isbn=978-3-540-42244-0|pmid=11987804}} The RNA segments are denoted Small (S), Medium (M; if present), and Large (L),{{cite journal|author=Pedersen IR|date=March 1973|title=Different classes of ribonucleic acid isolated from lymphocytic choriomeningitis virus|journal=J. Virol.|volume=11|issue=3|pages=416–23|doi=10.1128/JVI.11.3.416-423.1973|pmc=355116|pmid=4734917}} and code for four viral proteins in a unique ambisense coding strategy.{{cite journal|vauthors=Auperin DD, Romanowski V, Galinski M, Bishop DH|date=December 1984|title=Sequencing studies of pichinde arenavirus S RNA indicate a novel coding strategy, an ambisense viral S RNA|journal=J. Virol.|volume=52|issue=3|pages=897–904|doi=10.1128/JVI.52.3.897-904.1984|pmc=254611|pmid=6492264}}{{cite journal|vauthors=Auperin DD, McCormick JB|date=February 1989|title=Nucleotide sequence of the Lassa virus (Josiah strain) S genome RNA and amino acid sequence comparison of the N and GPC proteins to other arenaviruses|url=https://zenodo.org/record/1258276|journal=Virology|volume=168|issue=2|pages=421–5|doi=10.1016/0042-6822(89)90287-0|pmid=2916333}} For mammarenaviruses and reptarenaviruses, each RNA segment codes for two viral proteins in opposite orientation such that the negative-sense RNA genome serves as the template for transcription of a single mRNA and the positive-sense copy of the RNA genome templates a second mRNA. The separate coding sequences of the two viral proteins are divided by an intergenic region RNA sequence that is predicted to fold into a stable hairpin structure.{{cite journal|vauthors=Auperin DD, Galinski M, Bishop DH|date=April 1984|title=The sequences of the N protein gene and intergenic region of the S RNA of pichinde arenavirus|journal=Virology|volume=134|issue=1|pages=208–19|doi=10.1016/0042-6822(84)90286-1|pmid=6324469}}

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 replication.{{cite journal|vauthors=Auperin D, Dimock K, Cash P, Rawls WE, Leung WC, Bishop DH|date=January 1982|title=Analyses of the genomes of prototype pichinde arenavirus and a virulent derivative of Pichinde Munchique: evidence for sequence conservation at the 3' termini of their viral RNA species|journal=Virology|volume=116|issue=1|pages=363–7|doi=10.1016/0042-6822(82)90429-9|pmid=6278715}}{{cite journal|vauthors=Auperin DD, Compans RW, Bishop DH|date=August 1982|title=Nucleotide sequence conservation at the 3' termini of the virion RNA species of New World and Old World arenaviruses|journal=Virology|volume=121|issue=1|pages=200–3|doi=10.1016/0042-6822(82)90130-1|pmid=6287720}}{{cite journal|author=Mattsson L|year=1989|title=Chronic non-A, non-B hepatitis with special reference to the transfusion-associated form|journal=Scand J Infect Dis Suppl|volume=59|pages=1–55|doi=10.3109/inf.1988.20.suppl-59.01|pmid=2502835}}{{cite journal|vauthors=Hass M, Westerkofsky M, Müller S, Becker-Ziaja B, Busch C, Günther S|date=December 2006|title=Mutational analysis of the lassa virus promoter|journal=J. Virol.|volume=80|issue=24|pages=12414–9|doi=10.1128/JVI.01374-06|pmc=1676312|pmid=17005649}}{{cite journal|display-authors=etal|vauthors=Kranzusch PJ, Schenk AD, Rahmeh AA|date=November 2010|title=Assembly of a functional Machupo virus polymerase complex|journal=Proc. Natl. Acad. Sci. U.S.A.|volume=107|issue=46|pages=20069–74|bibcode=2010PNAS..10720069K|doi=10.1073/pnas.1007152107|pmc=2993349|pmid=20978208|doi-access=free}} The conserved 5' and 3' RNA termini sequences are complementary and allows each RNA segment to adopt a double-stranded RNA panhandle structure{{cite conference|vauthors=Bishop DH, Auperin DD|title=Arenavirus Gene Structure and Organization |year=1987|book-title=Arenaviruses|series=Current Topics in Microbiology and Immunology|volume=133|pages=5–17|doi=10.1007/978-3-642-71683-6_2|isbn=978-3-642-71685-0|pmid=2435460}} that maintains the termini in close proximity and results in a circular appearance to purified arenavirus genomic templates visualized by electron microscopy.{{cite journal|vauthors=Young PR, Howard CR|date=April 1983|title=Fine structure analysis of Pichinde virus nucleocapsids|journal=J. Gen. Virol.|volume=64|issue=4|pages=833–42|doi=10.1099/0022-1317-64-4-833|pmid=6682139|doi-access=free}}{{cite journal|vauthors=Palmer EL, Obijeski JF, Webb PA, Johnson KM|date=September 1977|title=The circular, segmented nucleocapsid of an arenavirus-Tacaribe virus|journal=J. Gen. Virol.|volume=36|issue=3|pages=541–5|doi=10.1099/0022-1317-36-3-541|pmid=199698|doi-access=free}} The double-stranded RNA panhandle structure is critical for efficient viral RNA synthesis,{{cite journal|vauthors=Perez M, de la Torre JC|date=January 2003|title=Characterization of the genomic promoter of the prototypic arenavirus lymphocytic choriomeningitis virus|journal=J. Virol.|volume=77|issue=2|pages=1184–94|doi=10.1128/jvi.77.2.1184-1194.2003|pmc=140842|pmid=12502835}} 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).{{cite journal|vauthors=Ghiringhelli PD, Rivera-Pomar RV, Lozano ME, Grau O, Romanowski V|date=September 1991|title=Molecular organization of Junin virus S RNA: complete nucleotide sequence, relationship with other members of the Arenaviridae and unusual secondary structures|journal=J. Gen. Virol.|volume=72|issue=9|pages=2129–41|citeseerx=10.1.1.325.5606|doi=10.1099/0022-1317-72-9-2129|pmid=1654373}} 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).{{cite journal|vauthors=Iapalucci S, López N, Rey O, Zakin MM, Cohen GN, Franze-Fernández MT|date=November 1989|title=The 5' region of Tacaribe virus L RNA encodes a protein with a potential metal binding domain|journal=Virology|volume=173|issue=1|pages=357–61|doi=10.1016/0042-6822(89)90257-2|pmid=2510403}}{{cite journal|display-authors=etal|vauthors=Iapalucci S, Lopez R, Rey O|date=May 1989|title=Tacaribe virus L gene encodes a protein of 2210 amino acid residues|journal=Virology|volume=170|issue=1|pages=40–7|doi=10.1016/0042-6822(89)90349-8|pmid=2718387}}{{cite journal|vauthors=Salvato MS, Shimomaye EM|date=November 1989|title=The completed sequence of lymphocytic choriomeningitis virus reveals a unique RNA structure and a gene for a zinc finger protein|journal=Virology|volume=173|issue=1|pages=1–10|doi=10.1016/0042-6822(89)90216-X|pmid=2510401}}

The Z protein forms homo oligomers and a structural component of the virions.{{cite journal|vauthors=Loureiro ME, D'Antuono A, Levingston Macleod JM, López N|date=September 2012|title=Uncovering viral protein-protein interactions and their role in arenavirus life cycle|journal=Viruses|volume=4|issue=9|pages=1651–67|doi=10.3390/v4091651|pmc=3499824|pmid=23170177|doi-access=free}} 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.{{cn|date=October 2022}}

File:Viruses-12-00784-g003.png

The glycoprotein (GP) is synthesised as a precursor molecule.{{cite journal|vauthors=Burri DJ, da Palma JR, Kunz S, Pasquato A|date=October 2012|title=Envelope glycoprotein of arenaviruses|journal=Viruses|volume=4|issue=10|pages=2162–81|doi=10.3390/v4102162|pmc=3497046|pmid=23202458|doi-access=free}} It is cleaved into three parts - GP1, GP2 and a stable signal peptide (SSP). These reactions are catalysed by cellular signal peptidases and the cellular enzyme Subtilisin Kexin Isozyme-1 (SKI-1)/Site-1 Protease (S1P). These processes are essential for fusion competence and incorporation of mature GP into nascent budding virion particles.{{cn|date=October 2022}}

Within the family Arenaviridae, arenaviruses were formerly all placed in the genus Arenavirus, but in 2015 were divided into the genera Mammarenavirus for those with mammalian hosts and Reptarenavirus for those infecting snakes.[http://www.ictvonline.org/proposals/2014.011a-dV.A.v2.Reptarenavirus.pdf ICTV proposals 2014.011a-dV et al.] {{Webarchive|url=https://web.archive.org/web/20160304115423/http://www.ictvonline.org/proposals/2014.011a-dV.A.v2.Reptarenavirus.pdf |date=4 March 2016 }}, Mark D. Stenglein et al.[http://www.ictvonline.org/proposals/2014.012aV.A.v3.Arenavirus_ren.pdf ICTV proposals 2014.012aV et al.] {{Webarchive|url=https://web.archive.org/web/20160304100809/http://www.ictvonline.org/proposals/2014.012aV.A.v3.Arenavirus_ren.pdf |date=4 March 2016 }}, Michael J. Buchmeier et al. Reptarenaviruses and mammarenavirus are separated by an impenetrable species barrier. Infected rodents cannot pass disease onto snakes, and IBD in captive snakes is not transmissible to humans.{{cn|date=October 2022}}

A third genus, Hartmanivirus (not to be confused with genus Haartmanvirus of vibrio phages in family Demerecviridae, order Caudovirales), has also been established,{{cite journal |vauthors=Stenglein MD, Sanders C, Kistler AL |title=Identification, characterization, and in vitro culture of highly divergent arenaviruses from boa constrictors and annulated tree boas: candidate etiological agents for snake inclusion body disease |journal=mBio |volume=3 |issue=4 |pages=e00180–12 |year=2012 |pmid=22893382 |pmc=3419519 |doi=10.1128/mBio.00180-12 |display-authors=etal}} including other species that infect snakes. The organisation of the genome of this genus is typical of arenaviruses but their glycoproteins resemble those of filoviruses. Species in this genus lack the matrix protein.{{cite journal |last1=Hepojoki |first1=Jussi |last2=Hepojoki |first2=Satu |last3=Smura |first3=Teemu |last4=Szirovicza |first4=Leonóra |last5=Dervas |first5=Eva |last6=Prähauser |first6=Barbara |last7=Nufer |first7=Lisbeth |last8=Schraner |first8=Elisabeth M. |last9=Vapalahti |first9=Olli |last10=Kipar |first10=Anja |last11=Hetzel |first11=Udo |title=Characterization of Haartman Institute snake virus-1 (HISV-1) and HISV-like viruses—The representatives of genus Hartmanivirus, family Arenaviridae |journal=PLOS Pathogens |date=2018 |volume=14 |issue=11 |page=e1007415 |doi=10.1371/journal.ppat.1007415 |pmid=30427944|pmc=6261641 |doi-access=free }}

A fourth genus, Antennavirus, has also been established{{cite web|url=https://ictv.global/taxonomy|title=Virus Taxonomy: 2019 Release|website=talk.ictvonline.org|publisher=International Committee on Taxonomy of Viruses|access-date=6 May 2020}} 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.{{cite journal |last1=Mordecai |first1=GJ |last2=Miller |first2=KM |last3=Di Cicco |first3=E |last4=Schulze |first4=AD |last5=Kaukinen |first5=KH |last6=Ming |first6=TJ |last7=Li |first7=S |last8=Tabata |first8=A |last9=Teffer |first9=A |last10=Patterson |first10=DA |last11=Ferguson |first11=HW |last12=Suttle |first12=CA |title=Endangered wild salmon infected by newly discovered viruses |journal=eLife |date=2019 |volume=8 |page=e47615|doi=10.7554/eLife.47615 |pmid=31478480 |pmc=6721791 |doi-access=free }}

Mammarenaviruses can be divided into two serogroups, which differ genetically and by geographical distribution:{{cite journal |vauthors=Delgado S, Erickson BR, Agudo R |title=Chapare virus, a newly discovered arenavirus isolated from a fatal hemorrhagic fever case in Bolivia |journal=PLOS Pathog. |volume=4 |issue=4 |pages=e1000047 |date=April 2008 |pmid=18421377 |pmc=2277458 |doi=10.1371/journal.ppat.1000047 |display-authors=etal |doi-access=free }}

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.

{{cite journal|journal=Genome Biology and Evolution|last1=Forni|first1=D|last2=Pontremoli|first2=C|last3=Pozzoli|first3=U|last4=Clerici|first4=M|last5=Cagliani|first5=R|last6=Sironi|first6=M

|title=Ancient evolution of Mammarenaviruses: Adaptation via changes in the L protein and no evidence for host-virus codivergence|doi=10.1093/gbe/evy050|pmid=29608723|volume=10|issue=3|pages=863–874|date=2018-03-01|access-date=2019-02-16|url=https://europepmc.org/abstract/pmc/pmc5863214|pmc=5863214}} 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.

File:Fimmu-10-00372-g001.jpg

{{Div col|colwidth=15em}}

• Alxa virus (ALXV)
• Bitu virus (BITV)
• Dandenong virus (DANV)
• Dhati Welel virus (DHWV)
• Gairo virus (GAIV)
• Gbagroube virus
• Ippy virus (IPPYV)
• Kitale virus (KTLV)
• Kodoko virus (KODV)
• Kwanza virus (KWAV)
• Lassa virus (LASV)
• Lìjiāng virus (LIJV)
• Loei River virus (LORV)
• Lujo virus(LUJV)
• Luna virus (LUAV)
• Lunk virus (LNKV)
• Lymphocytic choriomeningitis virus (LCMV)
• Mafiga virus (MAFV)
• Mariental virus (MRTV)
• Merino Walk virus (MRWV)
• Menekre virus
• Minu virus
• Mobala virus (MOBV)
• Mopeia virus (MOPV)
• Morogoro virus (MORV)
• Okahandja virus (OKAV)
• Ryukyu virus (RYKV)
• Solwezi virus (SOLV)
• Souris virus (SOUV)
• Wenzhou virus (WENV)

{{div col end}}

{{Div col|colwidth=15em}}

• Clade A
• Allpahuayo virus (AALV)
• Flexal virus (FLEV)
• Paraná virus (PRAV)
• Pichindé virus (PICHV)
• Pirital virus (PIRV)
• Clade B
• Amaparí virus (AMAV)
• Aporé virus (APOV)
• Chapare virus (CHAPV)
• Cupixi virus (CUPXV)
• Guanarito virus (GTOV)
• Junín virus (JUNV)
• Machupo virus (MACV)
• Ocozocoautla de Espinosa virus
• Real de Catorce virus (RCTV)
• Tacaribe virus (TCRV)
• Xapuri virus (XAPV)
• Sabiá virus (SBAV)
• Clade C
• Latino virus (LATV)
• Oliveros virus (OLVV)
• Clade D
• Bear Canyon virus (BCNV)
• Catarina virus (CTNV)
• Skinner Tank virus (SKTV)
• Tamiami virus (TMMV)
• Whitewater Arroyo virus (WWAV)
• Catarina virus (CTNV)
• Big Brushy Tank virus (BBTV)
• Skinner Tank virus (SKTV)
• Tonto Creek virus (TTCV)
• Others
• Patawa virus

{{div col end}}

• California reptarenavirus
• Giessen reptarenavirus
• Golden reptarenavirus
• Ordinary reptarenavirus
• Rotterdam reptarenavirus

• Haartman hartmanivirus
• Heimat hartmanivirus
• Muikkunen hartmanivirus
• Schoolhouse hartmanivirus
• Setpatvet hartmanivirus
• Zurich hartmanivirus

• Hairy antennavirus
• Salmon antennavirus
• Striated antennavirus

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.

Some arenaviruses are zoonotic 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.{{cn|date=October 2022}}

File:Fimmu-10-00372-g005.jpg

1. Lymphocytic choriomeningitis (LCM) viruses cause influenza-like febrile illness, but occasionally they may cause meningitis, characteristically accompanied by large numbers of lymphocytes in the cerebrospinal fluid (as the name LCM suggests).
2. Lassa virus causes Lassa fever. Lassa fever is endemic in west Africa. The virus was first isolated from Americans stationed in the village of Lassa, Nigeria. The virus can be transmitted person-to-person.
3. * Subclinical diseases: Serological studies suggest that inapparent infections particularly among members of hunting tribes are common.
4. * Clinical infections: Lassa fever is characterised by high fever, severe myalgia, coagulopathy, haemorrhagic skin rash, and occasional visceral haemorrhage as well as necrosis of liver and spleen.
5. Other Arenaviruses like Junin virus, Machupo virus cause haemorrhagic fevers.

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.

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.[https://news.yahoo.com/s/ap/20090529/ap_on_he_me/med_new_african_virus 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.{{cn|date=October 2022}}

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.{{Cite news|date=2020-10-10|title=Three women had organ transplants from one donor. They all died in the same week|url=https://www.abc.net.au/news/health/2020-10-11/nobody-knew-karens-donor-kidney-was-carrying-a-rare-virus/12743548|access-date=2020-10-11|newspaper=ABC News|language=en-AU}}{{cite web |url=http://www.news24.com/News24/South_Africa/News/0,,2-7-1442_2408685,00.html |title=Virus identified - nurse ill |access-date=2008-10-13 |publisher=News24.com |archive-url=https://web.archive.org/web/20081013152705/http://www.news24.com/News24/South_Africa/News/0%2C%2C2-7-1442_2408685%2C00.html |archive-date=13 October 2008 }}

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.{{cite web | url = http://www.theage.com.au/victoria/virus-kills-organ-recipients-20100915-15cn8.html | title = Virus kills organ recipients | access-date = 2009-10-16 | publisher = www.theage.com.au }}

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.{{Cite journal | last1 = Lee | first1 = A. M. | last2 = Pasquato | first2 = A. | last3 = Kunz | first3 = S. | doi = 10.1016/j.virol.2010.11.022 | title = Novel approaches in anti-arenaviral drug development | journal = Virology | volume = 411 | issue = 2 | pages = 163–169 | year = 2011 | pmid = 21183197 | pmc =3057354 }} 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.{{cite journal |doi=10.1128/AAC.01219-10 |title=T-705 (Favipiravir) Inhibition of Arenavirus Replication in Cell Culture |year=2010 |last1=Mendenhall |first1=M. |last2=Russell |first2=A. |last3=Juelich |first3=T. |last4=Messina |first4=E. L. |last5=Smee |first5=D. F. |last6=Freiberg |first6=A. N. |last7=Holbrook |first7=M. R. |last8=Furuta |first8=Y. |last9=De La Torre |first9=J.-C. |last10=Nunberg |first10=J. H. |last11=Gowen |first11=B. B. |journal=Antimicrobial Agents and Chemotherapy |volume=55 |issue=2 |pages=782–787 |pmid=21115797 |pmc=3028760 |display-authors=8 }}

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.

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.{{cite journal |author=Hadas Cohen-Dvashi |author2=Ron Amon |author3=Krystle N. Agans |author4=Robert W. Cross |author5=Aliza Borenstein-Katz |author6=Mathieu Mateo |author7=Sylvain Baize |author8=Vered Padler-Karavani |author9=Thomas W. Geisbert |author10=Ron Diskin |title=Rational design of universal immunotherapy for TfR1-tropic arenaviruses |journal= Nature Communications |volume=11 |issue=1 |pages=67 |year=2020 |doi=10.1038/s41467-019-13924-6|pmid=31900422 |pmc=6941993 |bibcode=2020NatCo..11...67C }}

{{Reflist}}

• [http://www.ictv.global/report/arenaviridae ICTV Report: Arenaviridae]
• [http://www.expasy.org/viralzone/all_by_species/83.html Viralzone: Arenavirus]
• [https://www.viprbrc.org/brc/home.spg?decorator=arena Virus Pathogen Database and Analysis Resource (ViPR): Arenaviridae]
• [http://www.vbrc.org Detailed genomic and bioinformatic information about Arenaviridae at NIH-funded database].
• [http://www.vbrc.org/query.asp?web_taxonomy=Arenaviridae Arenaviridae Genomes] {{Webarchive|url=https://web.archive.org/web/20170405211914/http://vbrc.org/query.asp?web_taxonomy=Arenaviridae |date=5 April 2017 }} database search results from the [http://www.vbrc.org Viral Bioinformatics Resource Center].
• [http://blog.google.org/2008/11/deadly-new-arenavirus.html Google.Org blog] info on recent outbreak.
• [http://www.stanford.edu/group/virus/arena/arenaviridae.html Arenaviruses]
• {{cite web |title=Arenavirus |publisher=NCBI Taxonomy Browser |url=https://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&id=11618 |id=11618 }}

{{Zoonotic viral diseases}}

{{Taxonbar|from=Q2368907}}

Category:Arthropod-borne viral fevers and viral haemorrhagic fevers