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| __NOTOC__
| | #redirect [[Lassa virus]] |
| <div style="float: right;">
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| {{Taxobox
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| | name = ''Lassa Virus (LASV)''
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| | image = Lassa virus.JPG
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| | image_width = 200 px
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| | image_caption = [[Transmission electron microscopy|TEM]] [[micrograph]] of ''Lassa virus'' [[Virion#Structure|virions]].
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| | virus_group = v
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| | ordo = ''Unassigned''
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| | familia = ''[[Arenavirus|Arenaviridae]]''
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| | genus = ''[[Arenavirus]]''
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| | species = '''''Lassa virus'''''
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| }}</div>
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| {{Lassa fever}}
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| {{CMG}}; {{AE}} {{Ammu}}
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| {{SK}} Lassa hemorrhagic fever; LHF
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| ==Overview==
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| Lassa fever is caused by the ''[[Lassa virus]]'', a member of the [[Arenaviridae]] family. It is an [[enveloped virus|enveloped]], [[single-stranded]], bisegmented [[RNA]] virus. Mastomysrodents shed the [[virus]] in [[urine]] and droppings. The direct contact with these materials or [[ingestion]] or [[inhalation]], can lead to [[infection]]. Lassa virus enters the [[cell]] by the receptor-mediated [[endocytosis]] and undergoes very rapid [[replication]] and manifest the [[disease]].
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| ==Virus==
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| ===Taxonomy===
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| * [[Viruses]]; [[ssRNA viruses]]; [[ssRNA negative-strand viruses]]; [[Arenaviridae]]; [[Mammarenavirus]] <ref>{{cite web | title = Taxonomy browser (Lassavirus) | url = http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&id=11621&lvl=3&keep=1&srchmode=1&unlock&lin=s}}</ref>
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| ===Biology===
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| * Lassa virus belongs to Arenaviridae <ref name=NCCN>{{cite web | title = The Centers for Disease Control and Prevention | url =http://www.cdc.gov/vhf/virus-families/arenaviridae.html }}</ref>.
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| * The Arenaviridae are a family of [[viruses]] whose members are generally associated with rodent-transmitted diseases in [[humans]]. Each [[virus]] usually is associated with a particular [[rodent]] host species in which it is maintained. [[Arenavirus]] infections are relatively common in humans in some areas of the world and can cause severe [[illnesses]].
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| [[File:Lassa fever micro.png|none|thumb|500px|Outbreak Distribution Map Lassa Fever CDC.png<SMALL><SMALL>''[http://www.cdc.gov/vhf/virus-families/arenaviridae.html]''<ref name="CDC">{{Cite web | title = Center for Disease Control and Prevention (CDC) | url = http://www.cdc.gov}}</ref></SMALL></SMALL>]]
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| ===Structure and genome===
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| * Lassa viruses are enveloped, [[single-stranded]], bisegmented, ambisense [[RNA viruses]]. Their genome<ref name="pmid10615121">{{cite journal| author=| title=Genome:The autobiography of a species in 23 chapters | journal=Nat Genet | year= 2000 | volume= 24 | issue= 1 | pages= 21 | pmid=10615121 | doi=10.1038/71638 | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=10615121 }} </ref> is contained in two RNA segments that code for two proteins each, one in each sense, for a total of four viral proteins.<ref name="pmid17143722">{{cite journal| author=Moshkoff DA, Salvato MS, Lukashevich IS| title=Molecular characterization of a reassortant virus derived from Lassa and Mopeia viruses. | journal=Virus Genes | year= 2007 | volume= 34 | issue= 2 | pages= 169-76 | pmid=17143722 | doi=10.1007/s11262-006-0050-3 | pmc=PMC1892610 | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=17143722 }} </ref> The large segment encodes a small zinc-binding protein (Z) that regulates transcription and replication,<ref name="pmid11533204">{{cite journal| author=Cornu TI, de la Torre JC| title=RING finger Z protein of lymphocytic choriomeningitis virus (LCMV) inhibits transcription and RNA replication of an LCMV S-segment minigenome. | journal=J Virol | year= 2001 | volume= 75 | issue= 19 | pages= 9415-26 | pmid=11533204 | doi=10.1128/JVI.75.19.9415-9426.2001 | pmc=PMC114509 | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=11533204 }} </ref><ref name="pmid9281522">{{cite journal| author=Djavani M, Lukashevich IS, Sanchez A, Nichol ST, Salvato MS| title=Completion of the Lassa fever virus sequence and identification of a RING finger open reading frame at the L RNA 5' End. | journal=Virology | year= 1997 | volume= 235 | issue= 2 | pages= 414-8 | pmid=9281522 | doi=10.1006/viro.1997.8722 | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=9281522 }} </ref> and the [[RNA polymerase]] (L). The small segment encodes the [[nucleoprotein]] (NP) and the surface [[glycoprotein precursor]] ([[GP]], also known as the viral spike), which is proteolytically cleaved into the [[envelope]] [[glycoproteins]] [[GP1]] and [[GP2]] that bind to the alpha-dystroglycan [[receptor]] and mediate [[host]] cell entry.<ref name="pmid11119613">{{cite journal| author=Smelt SC, Borrow P, Kunz S, Cao W, Tishon A, Lewicki H et al.| title=Differences in affinity of binding of lymphocytic choriomeningitis virus strains to the cellular receptor alpha-dystroglycan correlate with viral tropism and disease kinetics. | journal=J Virol | year= 2001 | volume= 75 | issue= 1 | pages= 448-57 | pmid=11119613 | doi=10.1128/JVI.75.1.448-457.2001 | pmc=PMC113937 | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=11119613 }} </ref>
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| * [[Lassa fever]] causes hemorrhagic [[fever]] frequently shown by [[immunosuppression]]. Replication for [[Lassa virus]] is very rapid, while also demonstrating temporal control in replication.<ref name="pmid16629503">{{cite journal| author=Lashley FR| title=Emerging infectious diseases at the beginning of the 21st century. | journal=Online J Issues Nurs | year= 2006 | volume= 11 | issue= 1 | pages= 2 | pmid=16629503 | doi= | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=16629503 }} </ref> The first replication step is transcription of [[mRNA]] copies of the negative- or minus-sense genome. This ensures an adequate supply of viral proteins for subsequent steps of replication, as the NP and L proteins are translated from the [[mRNA]]. The positive- or plus-sense [[genome]], then makes viral complementary [[RNA]] (vcRNA)copies of itself. The [[RNA]] copies are a template for producing negative-sense progeny, but [[mRNA]] is also synthesized from it. The [[mRNA]] synthesized from [[vcRNA]] are translated to make the GP and Z proteins. This temporal control allows the spike proteins to be produced last, and therefore, delay recognition by the host [[immune system]].
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| * [[Nucleotide]] studies of the [[genome]] have shown that Lassa has four lineages: three found in Nigeria and the fourth in Guinea, Liberia, and Sierra Leone. The Nigerian strains seem likely to have been ancestral to the others but additional work is required to confirm this.<ref name="pmid10888638">{{cite journal| author=Bowen MD, Rollin PE, Ksiazek TG, Hustad HL, Bausch DG, Demby AH et al.| title=Genetic diversity among Lassa virus strains. | journal=J Virol | year= 2000 | volume= 74 | issue= 15 | pages= 6992-7004 | pmid=10888638 | doi= | pmc=PMC112216 | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=10888638 }} </ref> One book that explains about this disease is The Lassa Ward by Ross I. Donaldson. He describes what it is like being a doctor and taking care of the Sierra Leone people who have contracted the virus.
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| [[File:Lassa virus micro.png|left|thumb|500px|Lassa Fever wikipedia.png<SMALL><SMALL>''[http://phil.cdc.gov/phil/details.asp]''<ref name="CDC">{{Cite web | title =wikipedia | url = http://phil.cdc.gov/phil/details.asp}}</ref></SMALL></SMALL>]]
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| ===Receptors===
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| * The [[Lassa virus]] gains entry into the [[host]] cell by means of the [[cell-surface receptor]] the alpha-[[dystroglycan]] (alpha-DG),<ref name="pmid10888638">{{cite journal| author=Bowen MD, Rollin PE, Ksiazek TG, Hustad HL, Bausch DG, Demby AH et al.| title=Genetic diversity among Lassa virus strains. | journal=J Virol | year= 2000 | volume= 74 | issue= 15 | pages= 6992-7004 | pmid=10888638 | doi= | pmc=PMC112216 | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=10888638 }} </ref> a versatile [[receptor]] for [[protein]]s of the [[extracellular matrix]]. It shares this [[receptor]] with the prototypic Old World [[arenavirus]] [[lymphocytic choriomeningitis]] virus. [[Receptor]] recognition depends on a specific sugar modification of alpha-dystroglycan by a group of [[glycosyltransferases]] known as the LARGE [[proteins]]. Specific variants of the [[genes]] encoding these [[proteins]] appear to be under positive selection inWest Africa where Lassa is endemic. [[Alpha-dystroglycan]] is also used as a [[receptor]] by [[viruses]] of the New World clade C [[arenaviruses]] (Oliveros and Latino viruses). In contrast, the New World [[arenaviruses]] of clades A and B, which include the important [[viruses]] Machupo, Guanarito, Junin, and Sabia in addition to the non pathogenic Amapari virus, use the [[transferrin]] receptor 1. A small aliphatic amino acid at the [[GP1]] [[glycoprotein]] [[amino acid]] position 260 is required for high-affinity binding to [[alpha-DG]]. In addition, [[GP1]] [[amino acid]] position 259 also appears to be important, since all [[arenaviruses]] showing high-affinity [[alpha-DG]] binding possess a bulky aromatic [[amino acid]] ([[tyrosine]] or [[phenylalanine]]) at this position.
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| * Unlike most enveloped viruses which use [[clathrin]] coated pits for cellular entry and bind to their [[receptors]] in a pH dependent fashion, Lassa and [[lymphocytic choriomeningitis virus]] instead use an [[endocytotic pathway]] independent of [[clathrin]], [[caveolin]], [[dynamin]] and [[actin]]. Once within the [[cell]] the [[viruses]] are rapidly delivered to [[endosomes]] via vesicular trafficking albeit one that is largely independent of the small GTPases Rab5 and Rab7. On contact with the [[endosome]] pH-dependent [[membrane fusion]] occurs mediated by the [[envelope]] [[glycoprotein]], which at the lower [[pH]] of the [[endosome]] binds the [[lysosome]] protein [[LAMP1]] which results in [[membrane]] [[fusion]] and escape from the [[endosome]].
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| ===Life cycle===
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| * The [[life cycle]] of Lassa virus is similar to the Old World [[arenaviruses]]<ref name=Wikipedia>{{cite web | title = Wikipedia lassa virus | url =http://en.wikipedia.org/wiki/Lassa_virus }}</ref>. Lassa virus enters the [[cell]] by the receptor-mediated [[endocytosis]]. Which [[endocytotic pathway]] is used is not known yet, but at least the cellular entry is sensitive to [[cholesterol]] depletion. It was reported that [[virus]] internalization is limited upon [[cholesterol]] depletion. The [[receptor]] used for [[cell entry]] is [[alpha-dystroglycan]], a highly conserved and ubiquitously expressed [[cell]] surface [[receptor]] for extracellular [[matrix proteins]].
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| * [[Dystroglycan]], which is later cleaved into [[alpha-dystroglycan]] and [[beta-dystroglycan]] is originally expressed in most [[cells]] to mature [[tissues]], and it provides molecular link between the [[ECM]] and the [[actin]]-based [[cytoskeleton]]<ref name="pmid18182084">{{cite journal| author=Rojek JM, Kunz S| title=Cell entry by human pathogenic arenaviruses. | journal=Cell Microbiol | year= 2008 | volume= 10 | issue= 4 | pages= 828-35 | pmid=18182084 | doi=10.1111/j.1462-5822.2007.01113.x | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=18182084 }} </ref>. After [[virus]] enters the [[cell]] by [[alpha-dystroglycan]] mediated [[endocytosis]], low-[[pH]] environment triggers [[pH]]-dependent [[membrane fusion]] and releases [[RNP]] (viral [[ribonucleoprotein]]) complex into the [[cytoplasm]]. Viral [[RNA]] is unpacked, and [[replication]] and [[transcription]] initiate in the [[cytoplasm]].<ref name="pmid18182084">{{cite journal| author=Rojek JM, Kunz S| title=Cell entry by human pathogenic arenaviruses. | journal=Cell Microbiol | year= 2008 | volume= 10 | issue= 4 | pages= 828-35 | pmid=18182084 | doi=10.1111/j.1462-5822.2007.01113.x | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=18182084 }} </ref> As the [[replication]] starts, both S and L [[RNA]] genomes synthesize the antigenomic S and L [[RNAs]], and from the antigenomic [[RNA]]s, genomic S and L [[RNA]] are synthesized. Both genomic and antigenomic RNAs are needed for [[transcription]] and [[translation]]. S [[RNA]] encodes [[GP]] and [[NP]] (viral [[nucleocapsid protein]]) [[proteins]], and L [[RNA]] encodes Z and L [[proteins]]. L [[protein]] most likely represents the viral RNA-dependent [[RNA polymerase]].<ref name="pmid12615304">{{cite journal| author=Drosten C, Kümmerer BM, Schmitz H, Günther S| title=Molecular diagnostics of [[viral hemorrhagic fevers]]. | journal=Antiviral Res | year= 2003 | volume= 57 | issue= 1-2 | pages= 61-87 | pmid=12615304 | doi= | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=12615304 }} </ref> When the [[cell]] is infected by the [[virus]], [[L polymerase]] is associated with the [[viral RNP]] and initiates the [[transcription]] of the [[genomic RNA]]. The 5’ and 3’ terminal 19 nt viral [[promoter]] regions of both [[RNA]] segments are necessary for recognition and binding of the [[viral polymerase]]. The primary [[transcription]] first transcribes [[mRNAs]] from the genomic S and L [[RNAs]], which code NP and L [[proteins]], respectively. [[Transcription]] terminates at the [[stem-loop]] (SL) structure within the intergenomic region. [[Arenaviruses]] use a cap snatching strategy to gain the cap structures from the cellular [[mRNAs]], and it is mediated by the [[endonuclease]] activity of the [[L polymerase]] and the cap binding activity of NP. [[Antigenomic RNA]] transcribes viral genes GPC and Z, encoded in genomic orientation, from S and L segments respectively. The [[antigenomic RNA]] also serves as the template for the replication.<ref name="pmid23202452">{{cite journal| author=Yun NE, Walker DH| title=Pathogenesis of Lassa fever. | journal=Viruses | year= 2012 | volume= 4 | issue= 10 | pages= 2031-48 | pmid=23202452 | doi=10.3390/v4102031 | pmc=PMC3497040 | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=23202452 }} </ref> After [[translation]] of GPC, it is posttranslationally modified in the [[endoplasmic reticulum]]. GPC is cleaved into [[GP1]] and [[GP2]] at the later stage of the secretory pathway. It is reported the cellular [[protease]] [[SKI-1]]/[[S1P]] was responsible for the [[cleavage]]. Cleaved [[glycoproteins]] are incorporated into the [[virion]] envelope when the [[virus]] buds and release from the [[cell membrane]].<ref name="pmid12615304">{{cite journal| author=Drosten C, Kümmerer BM, Schmitz H, Günther S| title=Molecular diagnostics of viral hemorrhagic fevers. | journal=Antiviral Res | year= 2003 | volume= 57 | issue= 1-2 | pages= 61-87 | pmid=12615304 | doi= | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=12615304 }} </ref>
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| ==Natural Reservoir==
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| * The [[reservoir]], or [[host]], of Lassa virus is a [[rodent]] known as the "multimammate rat" (Mastomys natalensis). Once infected, this rodent is able to [[excrete]] [[virus]] in [[urine]] for an extended time period, maybe for the rest of its life. Mastomys rodents breed frequently, produce large numbers of offspring, and are numerous in the savannas and forests of west, central, and east Africa. In addition, Mastomys readily colonize human homes and areas where food is stored. All of these factors contribute to the relatively efficient spread of Lassa virus from [[infected]] [[rodents]] to [[humans]].
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| * [[Transmission]] of Lassa virus to humans occurs most commonly through [[ingestion]] or [[inhalation]]. Mastomysrodents shed the [[virus]] in [[urine]] and droppings and direct contact with these materials, through touching soiled objects, eating contaminated [[food]], or exposure to open [[cuts]] or [[sores]], can lead to [[infection]].
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| * Because Mastomys rodents often live in and around homes and scavenge on leftover human food items or poorly stored food, direct contact [[transmission]] is common. Mastomys [[rodents]] are sometimes consumed as a food source and [[infection]] may occur when [[rodents]] are caught and prepared. Contact with the [[virus]] may also occur when a person inhales tiny particles in the air contaminated with infected [[rodent]] excretions. This [[aerosol]] or airborne [[transmission]] may occur during cleaning activities, such as sweeping.
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| * [[Direct]] contact with infected rodents is not the only way in which people are [[infected]]; person-to-person [[transmission]] may occur after exposure to [[virus]] in the [[blood]], [[tissue]], [[secretions]], or excretions of a Lassa virus-infected individual. Casual contact (including [[skin]]-to-[[skin]] contact without exchange of [[body fluids]]) does not spread Lassa virus. Person-to-person [[transmission]] is common in health care settings (called [[nosocomial transmission]]) where proper [[personal protective equipment]] (PPE) is not available or not used. Lassa virus may be spread in contaminated [[medical equipment]], such as reused needles.
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| ==Gallery==
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| The images below display key features of the Lassa virus.
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| <gallery>
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| Image:PHIL 2994 lores.jpg|This photomicrograph shows hepatitis caused by the Lassa virus, using toluidine-blue azure II stain. Source: CDC microbiologist Dr. W. Winn.<SMALL><SMALL>''[http://phil.cdc.gov/phil/details.asp Adapted from Public Health Image Library (PHIL), Centers for Disease Control and Prevention.]''<ref name="PHIL">{{Cite web | title = Public Health Image Library (PHIL), Centers for Disease Control and Prevention | url = http://phil.cdc.gov/phil/details.asp/}}</ref></SMALL></SMALL>
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| Image:Lassa virions.jpg|This highly magnified transmission electron micrograph (TEM) depicted some of the ultrastructural details of three Lassa virus virions.<SMALL><SMALL>''[http://phil.cdc.gov/phil/details.asp Adapted from Public Health Image Library (PHIL), Centers for Disease Control and Prevention.]''<ref name="PHIL">{{Cite web | title = Public Health Image Library (PHIL), Centers for Disease Control and Prevention | url = http://phil.cdc.gov/phil/details.asp}}</ref></SMALL></SMALL>
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| Image:Ebola virus3.png|Scanning electron micrograph (SEM) revealing ultrastructural morphologic features of the Ebola virus from the Ivory Coast of Africa.<SMALL><SMALL>''[http://phil.cdc.gov/phil/ Adapted from Public Health Image Library (PHIL), Centers for Disease Control and Prevention.]''<ref name="PHIL">{{Cite web | title = Public Health Image Library (PHIL), Centers for Disease Control and Prevention | url = http://phil.cdc.gov/phil/}}</ref></SMALL></SMALL>
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| Image:Ebola virus4.png|Negatively-stained transmission electron micrograph (TEM) demonstrating the ultrastructural curvilinear morphologic features displayed by the Ebola virus from the Ivory Coast of Africa.<SMALL><SMALL>''[http://phil.cdc.gov/phil/ Adapted from Public Health Image Library (PHIL), Centers for Disease Control and Prevention.]''<ref name="PHIL">{{Cite web | title = Public Health Image Library (PHIL), Centers for Disease Control and Prevention | url = http://phil.cdc.gov/phil/}}</ref></SMALL></SMALL></gallery>
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| ==References==
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| {{Reflist|2}}
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| [[Category:Hemorrhagic fevers]]
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| [[Category:Tropical disease]]
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| [[Category:Biological weapons]]
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