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Comment
. 2018 Oct 9;115(41):10201-10203.
doi: 10.1073/pnas.1814275115. Epub 2018 Sep 19.

Collusion Between Neutralizing Antibodies and Other Immune Factions in the Destruction of Adenoviral Vectors

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Free PMC article
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Collusion Between Neutralizing Antibodies and Other Immune Factions in the Destruction of Adenoviral Vectors

P J Klasse. Proc Natl Acad Sci U S A. .
Free PMC article

Conflict of interest statement

The author declares no conflict of interest.

Figures

Fig. 1.
Fig. 1.
Viruses are either enveloped (blue and cyan) or naked (red), but even the latter cover their genomes with a capsid; unencapsidated genomes, viroids, are not prominent parasites in the animal kingdom but are more so in plants. Some antiviral antibodies are neutralizing (black Y shapes); others are not (gray Y shapes; Non-NAb, nonneutralizing antibodies). Enveloped viruses enter cells by fusion of the viral envelope with the cell surface (orange) or with an endosomal membrane (purple). Neutralizing antibodies bind to the envelope glycoprotein on the virion surface (dark green) and prevent its interaction with receptors (orange) or later events in the fusion process. Naked viruses enter by membrane penetration at the cell surface or from an endosome, either translocating the whole capsid or just injecting the genome. Capsids of naked or enveloped viruses, once in the cytoplasm, can be attacked by receptors in the TRIM family. For naked viruses, TRIM21 (yellow) can mediate cytoplasmic neutralization of virions that are bound to antibodies (antibodies lack access to the capsid of enveloped viruses). With TRIM21 bound to antibodies on its surface, the capsid is destined for ubiquitination and degradation by the proteasome (gray cylinder). This process entails differential innate sensing, depending on whether the genome consists of RNA, sensed by RIG-I, assisted by the adaptor mitochondrial antiviral signaling protein (MAVS), or the genome consists of DNA, sensed by cGAS, aided by the adaptor STING. The proteolysis of the core proteins also exposes the viral genomes to cytoplasmic nucleases (7). Concurrently, the genome is destroyed and a cascade of immune signaling is launched.

Comment on

  • TRIM21 mediates antibody inhibition of adenovirus-based gene delivery and vaccination.
    Bottermann M, Foss S, van Tienen LM, Vaysburd M, Cruickshank J, O'Connell K, Clark J, Mayes K, Higginson K, Hirst JC, McAdam MB, Slodkowicz G, Hutchinson E, Kozik P, Andersen JT, James LC. Bottermann M, et al. Proc Natl Acad Sci U S A. 2018 Oct 9;115(41):10440-10445. doi: 10.1073/pnas.1806314115. Epub 2018 Sep 12. Proc Natl Acad Sci U S A. 2018. PMID: 30209217 Free PMC article.

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