TY - JOUR
T1 - Influenza virus uses transportin 1 for vRNP debundling during cell entry
AU - Miyake, Yasuyuki
AU - Keusch, Jeremy J.
AU - Decamps, Laure
AU - Ho-Xuan, Hung
AU - Iketani, Sho
AU - Gut, Heinz
AU - Kutay, Ulrike
AU - Helenius, Ari
AU - Yamauchi, Yohei
PY - 2019/4/1
Y1 - 2019/4/1
N2 - Influenza A virus is a pathogen of great medical impact. To develop novel antiviral strategies, it is essential to understand the molecular aspects of virus–host cell interactions in detail. During entry, the viral ribonucleoproteins (vRNPs) that carry the RNA genome must be released from the incoming particle before they can enter the nucleus for replication. The uncoating process is facilitated by histone deacetylase 6 (ref.1). However, the precise mechanism of shell opening and vRNP debundling is unknown. Here, we show that transportin 1, a member of the importin-β family proteins, binds to a PY-NLS2 sequence motif close to the amino terminus of matrix protein (M1) exposed during acid priming of the viral core. It promotes the removal of M1 and induces disassembly of vRNP bundles. Next, the vRNPs interact with importin-α/β and enter the nucleus. Thus, influenza A virus uses dual importin-βs for distinct steps in host cell entry.
AB - Influenza A virus is a pathogen of great medical impact. To develop novel antiviral strategies, it is essential to understand the molecular aspects of virus–host cell interactions in detail. During entry, the viral ribonucleoproteins (vRNPs) that carry the RNA genome must be released from the incoming particle before they can enter the nucleus for replication. The uncoating process is facilitated by histone deacetylase 6 (ref.1). However, the precise mechanism of shell opening and vRNP debundling is unknown. Here, we show that transportin 1, a member of the importin-β family proteins, binds to a PY-NLS2 sequence motif close to the amino terminus of matrix protein (M1) exposed during acid priming of the viral core. It promotes the removal of M1 and induces disassembly of vRNP bundles. Next, the vRNPs interact with importin-α/β and enter the nucleus. Thus, influenza A virus uses dual importin-βs for distinct steps in host cell entry.
KW - Influenza virus entry
KW - Cell biology
KW - Structural biology
KW - Traffic
UR - http://www.scopus.com/inward/record.url?scp=85060785624&partnerID=8YFLogxK
UR - https://naturemicrobiologycommunity.nature.com/users/202603-yohei-yamauchi/posts/43354-ribonuclear-penguins-go-viral
U2 - 10.1038/s41564-018-0332-2
DO - 10.1038/s41564-018-0332-2
M3 - Letter (Academic Journal)
C2 - 30692667
AN - SCOPUS:85060785624
SN - 2058-5276
VL - 4
SP - 578
EP - 586
JO - Nature Microbiology
JF - Nature Microbiology
IS - 4
ER -