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Review
. 2017 Jan 19;9(1):14.
doi: 10.3390/v9010014.

The IMPORTance of the Nucleus during Flavivirus Replication

Adam J Lopez-Denman  1   2 , Jason M Mackenzie  3
Affiliations
Review

The IMPORTance of the Nucleus during Flavivirus Replication

Adam J Lopez-Denman et al. Viruses. .

Abstract

Flaviviruses are a large group of arboviruses of significant medical concern worldwide. With outbreaks a common occurrence, the need for efficient viral control is required more than ever. It is well understood that flaviviruses modulate the composition and structure of membranes in the cytoplasm that are crucial for efficient replication and evading immune detection. As the flavivirus genome consists of positive sense RNA, replication can occur wholly within the cytoplasm. What is becoming more evident is that some viral proteins also have the ability to translocate to the nucleus, with potential roles in replication and immune system perturbation. In this review, we discuss the current understanding of flavivirus nuclear localisation, and the function it has during flavivirus infection. We also describe-while closely related-the functional differences between similar viral proteins in their nuclear translocation.

Keywords: flavivirus; karyopherins; nuclear localisation sequence; nuclear pore complex; nucleus; transport.

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Conflict of interest statement

The authors declare no conflict of interest. The founding sponsors had no role in the design or in the writing of the manuscript, and in the decision to publish the manuscript.

Figures

Figure 1
Figure 1
Representation of Flavivirus genome organisation. (a) Ten viral genes encode for three structural and seven non-structural (NS) viral proteins that are co- and post-translationally modified into mature viral proteins by host factors and the viral NS2B-3 protease complex [2]; (b) Viral protein subcellular localisation is generally cytoplasmic or associated with the endoplasmic reticulum (ER) membrane, due to the localisation of replication, but in specific viruses (listed), proteins such as NS5 can also localise to the nucleus.
Figure 2
Figure 2
Simplified nucleocytoplasmic protein transport. The nuclear envelope is the physical barrier between the nucleus and the cytoplasm, and is studded with channels known as nuclear pore complexes. For proteins to undergo nucleocytoplasmic transport, they require a nuclear localisation sequence (NLS) or nuclear export sequence (NES), and its corresponding karyopherin. Transport then occurs through the nuclear pore, with directionality determined through interactions with the Ran cycle. When in the cytoplasm, Ran is in a GDP bound state and can facilitate nuclear import. Once in the nucleus, the GDP gets converted to GTP and now can facilitate export [9].
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