vRNP Export through the nuclear pore

Stable Identifier
Reaction [dissociation]
Homo sapiens
Related Species
Influenza A virus
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Viral RNP, bound by M1 and NEP/NS2 interacting with CRM1, are shuttled through the nuclear pore into the cytoplasm (Martin, 1991; O'Neill, 1998; Buolo, 2006). This mechanism may resemble export of HIV-1 ribonucleoprotein, where the HIV-1 Rev export protein interacts with CRM1 (Askjaer, 1998). A number of cofactors are implicated in CRM1-mediated export, including the small GTPase Ran, Ran-binding proteins 1 and 3, and a guanine nucleotide exchange factor (Nilsson, 2001; Nemergut, 2002; Petosa, 2004). Ternary CRM1-cofactor-cargo complexes likely interact transiently with nuclear pore proteins (nucleoporins) as they traverse the pore (reviewed in Suntharalingam, 2003). RanGTP is hydrolyzed to RanGDP in the cytoplasm, an activity that can be stimulated by NEP/NS2 (Akarsu, 2003). Influenza infection activates Raf/MEK/ERK signaling, which is necessary for NEP/NS2-mediated export of viral RNP (Pleschka, 2001; Marjuki, 2006). Influenza vRNP complexes released into the cytoplasm do not re-enter the nucleus, as they are thought to remain bound by M1, preventing re-import (Martin, 1991). It has been suggested that M1 binding of zinc cations could distinguish M1 bound to the vRNP from polymerized, matrix M1 present in nascent virions (Elster, 1994).

Literature References
PubMed ID Title Journal Year
9837918 The specificity of the CRM1-Rev nuclear export signal interaction is mediated by RanGTP

Jensen, TH, Englmeier, L, Nilsson, J, Askjaer, P, Kjems, J

J Biol Chem 1998
17081640 Nuclear traffic of influenza virus proteins and ribonucleoprotein complexes

Baudin, F, Ruigrok, RW, Akarsu, H, Boulo, S

Virus Res 2006
15574331 Architecture of CRM1/Exportin1 suggests how cooperativity is achieved during formation of a nuclear export complex

Mattaj, IW, Bauer, U, Baudin, F, Muller, CW, Petosa, C, Steuerwald, U, Soler-Lopez, M, Schoehn, G, Askjaer, P, Moulin, M

Mol Cell 2004
11932251 Ran-binding protein 3 links Crm1 to the Ran guanine nucleotide exchange factor

Macara, IG, Lindsay, ME, Brownawell, AM, Nemergut, ME

J Biol Chem 2002
11451485 Inhibition of nuclear export of ribonucleoprotein complexes of influenza virus by leptomycin B

Takizawa, N, Katoh, M, Kobayashi, N, Nagata, K, Hoshida, K, Watanabe, K

Virus Res 2001
8113738 A small percentage of influenza virus M1 protein contains zinc but zinc does not influence in vitro M1-RNA interaction

Baudin, F, Ruigrok, RW, Cusack, S, Elster, C, Larsen, K, Fourest, E

J Gen Virol 1994
16608852 Membrane accumulation of influenza A virus hemagglutinin triggers nuclear export of the viral genome via protein kinase Calpha-mediated activation of ERK signaling

Wagner, R, Marjuki, H, Alam, MI, Ehrhardt, C, Klenk, HD, Planz, O, Ludwig, S, Pleschka, S

J Biol Chem 2006
11289803 Nuclear export of influenza virus ribonucleoproteins: identification of an export intermediate at the nuclear periphery

Whittaker, GR, Roy, AM, Ma, K

Virology 2001
11231581 Influenza virus propagation is impaired by inhibition of the Raf/MEK/ERK signalling cascade

Wolff, T, Rapp, UR, Ehrhardt, C, Planz, O, Ludwig, S, Pleschka, S, Hobom, G

Nat Cell Biol 2001
11124902 A role for the basic patch and the C terminus of RanGTP in regulating the dynamic interactions with importin beta, CRM1 and RanBP1

Askjaer, P, Nilsson, J, Kjems, J

J Mol Biol 2001
Event Information
This event is regulated
Name Identifier Synonyms
influenza DOID:8469 Influenza with other manifestations (disorder), Influenza with other manifestations NOS (disorder), flu, Influenza with other manifestations, Influenza with non-respiratory manifestation (disorder), influenza with non-respiratory manifestation
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