Lassavirus

Elektronmikrograf af nogle Lassavirus
Elektronmikrograf af nogle Lassavirus
Skitse af et ambipolært RNA-segment

Lassavirus eller Lassa mammarenavirus, LASV, er en virus i familien Arenaviridae, der forårsager Lassafeber, også kaldet Lassa-blødningsfeber eller Lassa hæmoragisk feber, en blødningssygdom med høj dødelighed.

Lassafeber er en zoonose, hvor virus overføres til mennesker fra rotter og andre gnavere. Lassafeber er endemisk i vestafrikanske lande, især Sierra Leone, Guinea, Nigeria og Liberia, hvor den årlige forekomst af infektion er mellem 300.000 og 500.000 tilfælde, hvilket resulterer i 5.000 dødsfald om året. Lassavirus kaldes sammen med Ebolavirus og Marburgvirus for de afrikanske blødningsfebervirus og klassificeres som virus i højeste fareklasse.[1][2][3][4]

Lassavirus er en indhyllet virus med en membrankappe og har et genom af enkeltstrenget ambipolariseret RNA i to segmenter.

I elektronmikroskop fremtræder Lassavirus som partikler i størrelsen 60–300 nm med et kornet udseende af ribosomer stammende fra værtscellen.

Inddeling

Arenavirus inddeles i to grupper:

  • OW - en gruppe i den gamle verden
  • NW - en gruppe i den nye verden, der underinddelse i tre klader (undergrupper): A, B og C

Genomet

Genom et er indeholdt i to enkeltstrengede, ambipolariserede RNA-segmenter, der hver koder for to proteiner, i alt fire virale proteiner. [5] Det store segment koder for et lille zinkfingerprotein (Z), der regulerer transkription og replikation, og RNA-polymerasen (L). Det lille segment koder for nukleoproteinet (NP) og overflade-glycoproteinet (GP, også kendt som Spike)[6]

Proteiner

  • Z, et lille zinkfingerprotein, der regulerer transkription og replikation
  • L, RNA-polymerase
  • NP, nukleoprotein
  • Spike-komplekset, som udgøres af tre proteolytiske fragmenter af GP (overflade-glykoprotein, forstadiet, GP-C). Spike-komplekset binder til receptorer iværtsorganismen, jvf. Spike
    • GP1 = receptor-binding subunit
    • GP2 = membrane-anchored fusion protein
    • SSP = structured signal peptide [7]

Receptor

OW såvel som NW klade C hæfter sig med Spike-proteinkomplekset til værtsorganismens alpha-dystroglycan (α-dystroglycan, α-DG).

NW klade A og B hæfter sig derimod til transferrin receptor 1 (TfR1 eller CD71), et membranprotein på værtsorganismens epithelceller.

Andet trin af celleinfektionsfasen sker i lysosomerne med membranfusion gennem lysosomproteinet LAMP1 i en pH-afhængig proces.[8]

Se også

Henvisninger

  1. ^ Lassafeber. Sundhed.dk
  2. ^ Lassafeber. Statens Seruminstitut
  3. ^ "Lassavirus. Center for Biosikring og Bioberedskab". Arkiveret fra originalen 10. november 2019. Hentet 2. juni 2020.
  4. ^ Lassa Feber Virus. Stanford University
  5. ^ Mammarenavirus. Viral Zone
  6. ^ Arenavirus Variations Due to Host-Specific Adaptation. MDPI 2013
  7. ^ Lassa virus glycoprotein signal peptide displays a novel topology with an extended endoplasmic reticulum luminal region. JBC 2004
  8. ^ Molecular Mechanism for LAMP1 Recognition by Lassa Virus. Journal of Virology 2015 (Webside ikke længere tilgængelig)

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Lassa virus.JPG

A transmission electron micrograph (TEM) of a number of Lassa virus virions adjacent to some cell debris. The virus, a member of the virus family en:Arenaviridae, causes en:Lassa fever.

Source:CDC's Public Health Image Library Image #8700

Photo Credit: C. S. Goldsmith
Polaritaet ambisense nl.png
Forfatter/Opretter: Gleiberg Rasbak, Licens: CC BY-SA 3.0
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Lassa virus virions TEM 8699 lores.jpg

ID#: 8699 Description: This highly magnified transmission electron micrograph (TEM) depicted some of the ultrastructural details of a number of Lassa virus virions adjacent to some cell debris. The virus, a member of the virus family Arenaviridae, is a single-stranded RNA virus, and is zoonotic, or animal-borne that can be transmitted to humans. The illness, which occurs in West Africa, was discovered in 1969 when two missionary nurses died in Nigeria, West Africa. In areas of Africa where the disease is endemic (that is, constantly present), Lassa fever is a significant cause of morbidity and mortality. While Lassa fever is mild or has no observable symptoms in about 80% of people infected with the virus, the remaining 20% have a severe multisystem disease. Lassa fever is also associated with occasional epidemics, during which the case-fatality rate can reach 50%.

Signs and symptoms of Lassa fever typically occur 1-3 weeks after the patient comes into contact with the virus. These include fever, retrosternal pain (pain behind the chest wall), sore throat, back pain, cough, abdominal pain, vomiting, diarrhea, conjunctivitis, facial swelling, proteinuria (protein in the urine), and mucosal bleeding. Neurological problems have also been described, including hearing loss, tremors, and encephalitis. Because the symptoms of Lassa fever are so varied and nonspecific, clinical diagnosis is often difficult.

Approximately 15%-20% of patients hospitalized for Lassa fever die from the illness. However, overall only about 1% of infections with Lassa virus result in death. The death rates are particularly high for women in the third trimester of pregnancy, and for fetuses, about 95% of which die in the uterus of infected pregnant mothers.