Viral penetration into host nucleus ~ ViralZone

Most DNA and few RNA viruses target their genome to the host nucleus. The crossing of nuclear membrane occurs in several ways :
-RNA virus, dsDNA virus and lentivirus genomes enter via the nuclear pore complex (NPC) through the cellular Importin transport.
-ssDNA virus capsid seems to be small enough to cross the NPC and enter the nucleus as an intact capsid.
-Hepadnaviridae capsid would enter the NPC pore, but remains attached to it and releases the viral genomic DNA into the nucleoplasm.
-Herpesvirales capsid is too large to enter the NPC pore, the viral genome is directly injected through the NPC on which the capsid docks.
-All retroviridae except lentivirus would enter the nucleus during mitosis, when the nuclear membrane temporarily disintegrates.

All these strategies to cross the nuclear envelope barrier are associated with various levels of capsid disassembly, since virus can pass intact (e.g. parvoviridae) or, in the case of injection, only the viral genome enters the nucleus (e.g. herpesviruses). Genome integration in the host genome may eventually follow .

Family	Virus	Viral protein	Host protein	Process
Herpesviridae	HSV-1	capsid	Importin-beta	capsid docking at nuclear pore
		capsid	Nup358	capsid docking at nuclear pore
		pUL25, capsid	Nup214	capsid docking at nuclear pore; DNA release
		pUL25	hCG1 (NUPL-2)	binds free pUL25; might be involved in capsid docking at nuclear pore
		pUL25	unknown, likely NPC component	uncoating of DNA at the NPC; soluble pUL25 inhibited uncoating but not NPC docking
Polyomaviridae	SV40	VP1/2/3	general nuclear transport machinery	capsid delivery to the nucleus; all VPs contain classical NLSs which likely use the importin-alpha/beta pathway
		VP1 pentamer	caspase-6, Lamin A/C	disruption of nuclear lamins by caspase-6 in order for capsids to penetrate INM from ER; fluctuations in Lamin A/C levels and associated phosphorylation at an unidentified residue in quiescent cells
Adenoviridae	Ad2/5		Crm1, Hsp70	nuclear targeting of capsids
	Ad2		Nup214, Importin-beta and importin-7, Histone H1	nuclear targeting of capsids via adapter protein histone H1
		hexon	Nup214/62/358	capsids bind Nup214/88/358 to dock at the NPC; Nup358 recruits kinesin heavy chain Kif5c to promote capsid disintegration; simultaneously leads to NPC perturbation
		pVII	Importin-alpha/beta, Importin-7, Transportin-1	nuclear import of Ad genomic DNA post-docking
		hexon	Importin-alpha/beta, Nups	nuclear docking of capsids
Baculo-viridae	AcMNPV		Importin-beta	nuclear delivery of capsids
Parvo-viridae	MVM		proteasome	nuclear delivery of capsids
			Caspase-3, lamin B2	NE disruption (ONM) by digestion of lamin B2

	wtAAV2		unknown	(unknown mechanism but independent from trafficking through the NPC)
	recAAV2		Importin-beta, Importin-7, NPC	nuclear delivery of capsids
	H1		Nup62, Nup153, Nup214, Nup358, PKCa, Cdk1/2, Caspase-3, Lamins	binding to NPC via alternative mechanism leads to subsequent disruption of the ONM and INM via the mitotic kinase-protease axis
Orthomyxoviridae	Influenza A	NP	Importin-a	nuclear import of vRNP
		NP	Importin-a1 or 2 + Importin-beta	nuclear import of vRNP
		NP	Transportin-3	nuclear import of vRNP (RNAi)
			CSE1L, KPNB 1, NUP214,NUP153, TNPO3	potentially nuclear import of vRNP (RNAi)
			Importin-beta, Crm1, Nup98, Nup205	potentially nuclear import of vRNP (RNAi)
			Importin-5	likely nuclear import of vRNP as delayed gene expression
		PB1/2, NP, PA + NS1	Importin-a4
		PB1/2, NP, PA	Importin-a7
Retroviridae	HIV-1	Vpr	hCG1, Nup54, Importin-alpha/beta	NEBD if Vpr overexpressed; greatly improves docking of the PIC at the NPC by directly binding to nucleoporins; increased affinity of importin-alpha/beta to the PIC; Vpr at the NE promotes G2 arrest/apoptosis
		Integrase	Nup62	chromatin associated Nup62 to aid genome integration
		Integrase	Importin-7	nuclear transport of pre-integration complex (PIC)
		Integrase	Nup98	reduction of genome integration
		Integrase	Importin-a1	nuclear import of PIC
		Integrase	Importin-a3	nuclear import of PIC into T cell nuclei
		Integrase, CA	Transportin-3	nuclear import of PIC
		CA	Nup153, Nup155	nuclear import of PIC
		CA	Nup358	targeting of imported PIC and increased efficiency of integration in transcriptionally active areas
		Matrix		nuclear import of PIC into non-dividing cells
	MLV	CA protein	masking of receptor binding site	inhibits nuclear transport of PIC
Hepadna-viridae	HBV	core protein	importin alpha/beta, Nup153	capsid entry to the nucleus and capsid arrest at Nup153 acts as a maturity checkpoint (coupled potentially to phosphorylation state)

Source: Viruses and the nuclear envelope,Thomas Hennig, Peter O'Hare, Curr. Opin. Cell Biol. June 2015; 34: 113.121

Viral penetration into host nucleus (kw:KW-1163)

Matching UniProtKB/Swiss-Prot entries

Capsid protein (Core antigen) (Core protein) (HBcAg) (p21.5)

Capsid vertex component 2

Large delta antigen (L-HDAg) (p27)

Nucleoprotein (Nucleocapsid protein) (Protein N)

Pre-histone-like nucleoprotein (Pre-core protein VII) (pVII)

Gag-Pol polyprotein (Pr160Gag-Pol)

Small delta antigen (S-HDAg) (p24)

Minor capsid protein L2

Minor capsid protein VP2 (Minor structural protein VP2)

Protein Vpr (R ORF protein) (Viral protein R)