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. Author manuscript; available in PMC: 2010 Aug 11.
Published in final edited form as: Nature. 2010 Feb 11;463(7282):813–817. doi: 10.1038/nature08699

Table 1.

Selected functional categories in early steps of influenza virus replication

Functional
Category		 Gene Names a Cellular function Proposed/known role in influenza virus
replication b 		Replication
block
IP3-PKC pathway ROCK1, CDC42BPA, KSR2, ARAF,
PRKCI, CDC42BPB, CIT, AKAP13,
RACGAP1, EIF2AK2, CDK4, ACVR2A,
MAPK1, PRKCD, MAP2K2, GRK5,
ARAF, HIPK1, PAK3, MAP2K3,
PTPMT1, LIMK1, PIP5K1C, PAK2,
GRK6, SGK1		 Signaling Viral entry, promoting apoptosis; inhibitors of
PKC block viral RNA replication and PKC
activators enhance virus replication		 Entry
(MAP2K3)
COPI vesicles ARCN1, COPA, COPB2, COPG, USE1 early endosome
maturation,
retrograde golgi to
ER transport		 entry (endosomal trafficking) Entry
(ARCN1)
Endosomal
uptake,
maturation,
acidification and
fusion 		ATP6V1A, ATP6V1B2, ATP6V0B,
ATP6V0C, ATP6AP1, ATP6V0D1,
ATP6AP2, RABEP1, PIP5K1C, VPS16,
TRPV2, MARCH2, EPHB2		 vATPase complex:
acidification of
intracellular
organelles, including
endosomes		 Low pH-dependent entry, ubiquitin/vacuolar
protein sorting pathway required for entry		 Entry
(ATP6V1A,
ATP6V1B2,
ATP6V0B,
ATP6V0C,
ATP6AP1)
Actin
organization and
function 		GAK, APC2, CIT, PAK2, CDC42BPB,
PAK3, CDC42BPA, SGCA, FSCN1,
OXSR1, CD81, FGFR2, FGFR4, ITGA3,
AKAP13, ACTC1, FGFR1, LIMK1, ROCK1,
PIK3R4		 Actin organization
and function		 Intracellular transport, Particle movement at
cell periphery prior to virus fusion; Actin also
implicated in NP functions such as
transcription, replication, and genome-
trafficking		 Entry (CD81,
FGFR2
FGFR4,
ITGA3,
AKAP13)
PI3K–AKT
pathway 		AKT1, BCL3, FRAP1, GSK3B, HRAS,
HSP90AA1, IKBKE, ITGA3, JAK2,
MAP2K2, MAPK1, MDM2, PIK3R4,
PIK3R4		 Signaling important for viral protein yields and nuclear
export of vRNPs. Involved in inhibition of
apoptosis.		 Entry
(GSK3B)
Endosomal
recycling
pathway 		RAB11B, RAB17 Vesicle trafficking entry (endosomal trafficking) Entry
(RAB11B)
MAPK pathway MAP2K3, DUSP3, MAP3K12,
MAPK1/ERK, MAP2K2/MEK, ARAF, CAD,
CREB1, EPHB2, FGFR4, HRAS, JUN,
NTRK2, PAK2, PRKACA, PRKCD,
MAP2K5, MAP4K4, HIPK3, ATP6AP2,
STK39, MINK1, PBK, TAOK1, ZNF436,
CANT1, KSR2		 Signaling important for viral protein yields and nuclear
export of vRNPs.		 Entry
(MAP2K3,
DUSP3)
Proteases CTSW, PCSK7, KLK9, ANPEP, PRSS35 Post-translational
processing		 HA cleavage Post-entry
(PRSS35)
Calcium/
Calmodulin
Proteins 		CAMK2B, PRKACA, DAPK2, ADRA1B,
CREB1, PRKAG2, DCLK2, GRK5, GRK6,
KCNJ3, PKD1, PRKCD, STX5, CACGN4,
AGTRAP		 Calcium regulation
and signaling		 Transcriptional regulation Post-entry
(CAMK2B)
Nuclear
trafficking 		CSE1L, KPNB1, NUP214, NUP153,
TNPO3		 Nuclear trafficking Nuclear import of vRNA or viral/host proteins Post-entry
(KPNB1,
CSE1L)
Trafficking STX10, STX5, GOPC, CLL1, NRBP1 Membrane and
Receptor trafficking		 Glycoprotein trafficking ND
Sumoylation SUMO2, SUMO1, SAE1, SUMO4 Post-translational
modification		 unknown ND
Microtubule
organization and
function 		MID1IP1, TUBB, PRKCI, PLK4, MARK2,
DCLK1, NUDCD3, RACGAP1, MAP1LC3C		 Cytoskeletal
organization		 Microtubules implicated in intracellular viral
transport.		 ND
Autophagy PRKAG2, MAP1LC3C, FRAP1, HRAS Stress response post-entry, blocks viral protein production ND
Ubiquitination MDM2, UBQLN4, HECTD1, CBLL1, DTX2,
EPS8L3, FBXO44		 Post-translational
modification		 unknown ND
a, b

References are contained in Supplemental Table 5. ND = No Data