Bourbon virus infection pathophysiology
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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-in-Chief: Syed Hassan A. Kazmi BSc, MD [2]
Overview
Pathophysiology
Bourbon virus is a negative sense segmented RNA virus belonging to the genus Thogotovirus, family Orthomyxovirida.
Transmission
- Boubon virus is transmitted mainly by ticks.
- The virus is able to replicate in vertebrate and tick cells.
Adherence
- Virus attaches to the N-acetylneuraminic acid component found in host cell membrane (sialic acid receptors).[1]
Endocytosis
- The virus gets endocytosed by clathrins into the host cell.
- Endosome acidification induces fusion of virus membrane with the vesicle membrane.
Virology and replication
- Thogoto viruses are spherical, enveloped single stranded RNA viruses with a segmented genome.
- Virions are 80-120nm in diameter with a genome size of approximately 10Kb. The 6-7 segments of genome encodes for 7-9 proteins with each segment size ranging from a low of 0.9Kb to 2.3Kb.
- Viral RNA polymerases (PA, PB1 and PB2) transcribe one mRNA from each gnome segment .
- Splicing of segment 6 mRNA gives rise to mRNA coding for the matrix protein M1.
- Transcription of genomic segments by the viral polymerase produces mRNAs that are capped and polyadenylated by the viral polymerase.
- The M1 protein is involved in export of genome from the nucleus.
- Assembly of the virus takes place in the cytoplasm from where new virions are released to infect other cells.
Host response
- Thogoto Virus Infection induces a sustained type 1 interferon response in the host until the daptive immunity takes effect.[2]
- IFN expression is mediated by specialized plasmacytoid dendritic cells (pDC).
- The interferon-induced dynamin-like MxA protein is involved in host antiviral activity against thogoto viruses.[3][4][5]
- MxA recognizes the nucleocapsids of invading viruses, causing an early block of the viral replication cycle.[3][6]
References
- ↑ "Receptor-Mediated Endocytosis and the Sorting of Internalized Proteins - Molecular Cell Biology - NCBI Bookshelf".
- ↑ Kochs G, Bauer S, Vogt C, Frenz T, Tschopp J, Kalinke U, Waibler Z (2010). "Thogoto virus infection induces sustained type I interferon responses that depend on RIG-I-like helicase signaling of conventional dendritic cells". J. Virol. 84 (23): 12344–50. doi:10.1128/JVI.00931-10. PMC 2976394. PMID 20861272.
- ↑ 3.0 3.1 Patzina C, Haller O, Kochs G (2014). "Structural requirements for the antiviral activity of the human MxA protein against Thogoto and influenza A virus". J. Biol. Chem. 289 (9): 6020–7. doi:10.1074/jbc.M113.543892. PMC 3937669. PMID 24448803.
- ↑ Haller O, Kochs G (2011). "Human MxA protein: an interferon-induced dynamin-like GTPase with broad antiviral activity". J. Interferon Cytokine Res. 31 (1): 79–87. doi:10.1089/jir.2010.0076. PMID 21166595.
- ↑ Frese M, Kochs G, Meier-Dieter U, Siebler J, Haller O (1995). "Human MxA protein inhibits tick-borne Thogoto virus but not Dhori virus". J. Virol. 69 (6): 3904–9. PMC 189115. PMID 7745744.
- ↑ Pavlovic J, Haller O, Staeheli P (1992). "Human and mouse Mx proteins inhibit different steps of the influenza virus multiplication cycle". J. Virol. 66 (4): 2564–9. PMC 289059. PMID 1548781.