Viral penetration into host nucleus


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 .

FamilyVirusViral proteinHost proteinProcessReference
HerpesviridaeHSV-1capsidImportin-betacapsid docking at nuclear pore
capsidNup358capsid docking at nuclear pore
pUL25, capsidNup214capsid docking at nuclear pore; DNA release
pUL25hCG1 (NUPL-2)binds free pUL25; might be involved in capsid docking at nuclear pore
pUL25unknown, likely NPC componentuncoating of DNA at the NPC; soluble pUL25 inhibited uncoating but not NPC docking
PolyomaviridaeSV40VP1/2/3general nuclear transport machinerycapsid delivery to the nucleus; all VPs contain classical NLSs which likely use the importin-alpha/beta pathway
VP1 pentamer caspase-6, Lamin A/Cdisruption 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
AdenoviridaeAd2/5Crm1, Hsp70nuclear targeting of capsids
Ad2Nup214, Importin-beta and importin-7, Histone H1nuclear targeting of capsids via adapter protein histone H1
hexonNup214/62/358capsids bind Nup214/88/358 to dock at the NPC; Nup358 recruits kinesin heavy chain Kif5c to promote capsid disintegration; simultaneously leads to NPC perturbation
pVIIImportin-alpha/beta, Importin-7, Transportin-1nuclear import of Ad genomic DNA post-docking
hexonImportin-alpha/beta, Nupsnuclear docking of capsids
Baculo-viridaeAcMNPVImportin-betanuclear delivery of capsids
Parvo-viridaeMVMproteasomenuclear delivery of capsids
Caspase-3, lamin B2NE disruption (ONM) by digestion of lamin B2
wtAAV2unknown (unknown mechanism but independent from trafficking through the NPC)
recAAV2Importin-beta, Importin-7, NPCnuclear delivery of capsids
H1Nup62, Nup153, Nup214, Nup358, PKCa, Cdk1/2, Caspase-3, Laminsbinding to NPC via alternative mechanism leads to subsequent disruption of the ONM and INM via the mitotic kinase-protease axis
OrthomyxoviridaeInfluenza ANPImportin-anuclear import of vRNP
NPImportin-a1 or 2 + Importin-betanuclear import of vRNP
NPTransportin-3nuclear import of vRNP (RNAi)
CSE1L, KPNB 1, NUP214,NUP153, TNPO3potentially nuclear import of vRNP (RNAi)
Importin-beta, Crm1, Nup98, Nup205potentially nuclear import of vRNP (RNAi)
Importin-5likely nuclear import of vRNP as delayed gene expression
PB1/2, NP, PA + NS1Importin-a4
PB1/2, NP, PAImportin-a7
RetroviridaeHIV-1VprhCG1, Nup54, Importin-alpha/betaNEBD 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
IntegraseNup62chromatin associated Nup62 to aid genome integration
IntegraseImportin-7nuclear transport of pre-integration complex (PIC)
IntegraseNup98reduction of genome integration
IntegraseImportin-a1nuclear import of PIC
IntegraseImportin-a3nuclear import of PIC into T cell nuclei
Integrase, CATransportin-3nuclear import of PIC
CANup153, Nup155nuclear import of PIC
CANup358targeting of imported PIC and increased efficiency of integration in transcriptionally active areas
Matrix nuclear import of PIC into non-dividing cells
MLVCA proteinmasking of receptor binding siteinhibits nuclear transport of PIC
Hepadna-viridaeHBVcore proteinimportin alpha/beta, Nup153capsid 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