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Review
. 2022 Mar 3;14(3):521.
doi: 10.3390/v14030521.

The Role of Nucleoprotein in Immunity to Human Negative-Stranded RNA Viruses-Not Just Another Brick in the Viral Nucleocapsid

Maja Šantak  1 , Zrinka Matić  1
Affiliations
Review

The Role of Nucleoprotein in Immunity to Human Negative-Stranded RNA Viruses-Not Just Another Brick in the Viral Nucleocapsid

Maja Šantak et al. Viruses. .

Abstract

Negative-stranded RNA viruses (NSVs) are important human pathogens, including emerging and reemerging viruses that cause respiratory, hemorrhagic and other severe illnesses. Vaccine design traditionally relies on the viral surface glycoproteins. However, surface glycoproteins rarely elicit effective long-term immunity due to high variability. Therefore, an alternative approach is to include conserved structural proteins such as nucleoprotein (NP). NP is engaged in myriad processes in the viral life cycle: coating and protection of viral RNA, regulation of transcription/replication processes and induction of immunosuppression of the host. A broad heterosubtypic T-cellular protection was ascribed very early to this protein. In contrast, the understanding of the humoral immunity to NP is very limited in spite of the high titer of non-neutralizing NP-specific antibodies raised upon natural infection or immunization. In this review, the data with important implications for the understanding of the role of NP in the immune response to human NSVs are revisited. Major implications of the elicited T-cell immune responses to NP are evaluated, and the possible multiple mechanisms of the neglected humoral response to NP are discussed. The intention of this review is to remind that NP is a very promising target for the development of future vaccines.

Keywords: B-cell immune response; T-cell immune response; negative-stranded RNA viruses; nucleoprotein; vaccines.

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Conflict of interest statement

The authors declare no conflict of interest.

Figures

Figure 1
Figure 1
Basic schematic representation of the virion structures of the negative-stranded RNA viruses. Structural proteins are shown. Some genera-specific proteins are omitted from the representation for simplicity (created with BioRender.com, accessed on 21 December 2021).
Figure 2
Figure 2
Schematic presentation of the transcription and translation processes with the RNA abundance gradient.
Figure 3
Figure 3
Distribution of amino acid substitutions in the mumps virus NP. Variability of the 82 mumps virus NP sequences from GenBank was analyzed. WebLogo was used to generate mumps virus nucleoprotein sequence logos (Crooks et al., 2004, https://weblogo.berkeley.edu/, accessed on 13 January 2022). Amino acid single letter annotation was used for each position in the sequence. The height of the column denotes the conservation of each amino acid position, while the height of the amino acid letter within the column indicates the relative frequency. Variability of each amino acid position is indicated below each logo panel.
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