Table 1.

Summary of respiratory virus protein interactions with components of the host nucleocytoplasmic transport system.

Virus	Viral Protein	Host protein	Effect of interaction	Effect of disrupting interaction on virus titre	Reference
Rhinovirus	2A	nup62	Disruption of host nucleocytoplasmic transport	N/A	Gustin and Sarnow (2002)
	2A	nup98
	2A/3C	nup153
	2A/3C	nup214/358
RSV	M	IMPβ1	IMPβ1 transports M to nucleus to initiate host-cell transcriptional inhibition and increase virus production	Mutation of M NLS results in 20-fold reduction in virus titre	Ghildyal et al. (2005a)
	M	XPO1	Nuclear export of M by XPO1 is absolutely essential to initiate virion formation	Mutation of M NES abolishes RSV virus production; inhibition of XPO1 mediated nuclear export using the XPO1 inhibitor LMB reduces RSV titre > 10-fold	Ghildyal et al. (2009a)
Influenza	NP	IMPα1, IMPα5	NP binding to α1 or β5 allows nuclear import of NP through Impβ1	Cells treated with peptides that compete with NP binding for Impα show 2–5 log reduction in Flu virus titre. Granzyme K mediated proteolysis of Impα/β reduced NP nuclear import and subsequent Flu viral titre twofold	O’Neill et al. (1995), Cros et al. (2005)
	PB1	IMPβ3	PB1 (heterodimer with PA) binds to IMPβ3 and is trafficked to the nucleus	Mutation of the IMPβ3 recognised NLS in PB1 results in a 4-log10 reduction in virus titre	Hutchinson et al. (2011)
	PB2	IMPα1, α3, α5, α7	PB2 shows preference for IMPβ7 in mammalian cells in vivo, but it can bind to IMPα3 and α5	Mutation of PB2 NLS results in 100-fold reduction in virus titre	Resa-Infante et al. (2008), Boivin and Hart (2011), Pumroy et al. (2015)
	PA	IMPβ3	Requires heterodimerization with PB1 to undergo nuclear import by IMPβ3	Mutation of the IMPβ3 recognised NLS in PB1 results in a 4-log10 reduction in virus titre	Hutchinson et al. (2011)
	NS2 (NEP)	XPO1	Allows nuclear export of vRNP-M1-NS2 complex from nucleus to cytoplasm where viral budding occurs	The XPO1 inhibitor LMB almost completely suppresses influenza virus levels in infected MDCK cells. XPO1 inhibitor Verdinexor inhibits influenza virus A and B replication in tissue culture and a mouse model.	Watanabe et al. (2008), Brunotte et al. (2014), Gao et al. (2014), Perwitasari et al. (2014)
	M1	IMPα1 (porcine)	M1 shows interaction with porcine IMPα1, but this has yet to be confirmed in human cells	N/A	Liu et al. (2014)
		Exporter (?)	Leucine-rich NES region identified in M1. Mutation causes accumulation of vRNP in the nucleus, even in the presence of NS2	Alanine mutation of the M1 NES reduced Flu viral titre 200–300-fold	Cao et al. (2012)
	vRNP-M1-NS2	Hsc70	Hsc70 has been shown to interact with M1 and may help mediate vRNP nuclear export in the absence of NS2		Watanabe et al. (2014)
		NXF1/TAP	NXF1/TAP is required for the nuclear export of viral mRNA encoding HA, NA, M1, NS1, and M2	siRNA depletion of NXF1 reduced Flu viral titre 100-fold	Read and Digard (2010)

IMP, importin; nup, nucleoporin; LMB, leptomycin B.