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  • Review Article
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Immune evasion by Kaposi's sarcoma-associated herpesvirus

Nature Reviews Immunology volume 7, pages 391–401 (2007)Cite this article

Key Points

  • Kaposi's sarcoma associated herpesvirus (KSHV) establishes persistent infection in its host and is associated with the development of Kaposi's sarcoma, as well as several lymphoproliferative disorders.

  • To persist in its host, KSHV devotes a considerable amount of its coding potential to encode for proteins that alter both innate and adaptive immune responses.

  • Most of these immunomodulatory genes have been acquired during evolution through molecular piracy. Some are homologous to cytokines, interferon-regulatory factors, complement regulatory proteins, whereas others are homologous to host proteins with unknown function.

  • Animal models represent important systems for the study of KSHV immune evasion, as KSHV replicates poorly in tissue culture and has a narrow host range. These animal models include the mouse herpesvirus 68 and the rhesus monkey rhadinovirus.

Abstract

To efficiently establish a persistent infection, Kaposi's sarcoma-associated herpesvirus (KSHV; also known as HHV8) dedicates a large amount of its coding potential to produce proteins that antagonize the immune system of its host. These viral immunomodulators interfere with both the innate and adaptive immune responses and most of them are homologous to cellular proteins, suggesting that they have been pirated from the host during viral evolution. In this Review, I present recent advances in the understanding of immune evasion by KSHV, with a particular focus on the virally encoded modulators of immune responses that are unique to this virus.

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Figure 1: KSHV genome map.
Figure 2: Inhibition of the type I interferon pathway by KSHV.
Figure 3: Ubiquitylation and degradation of MHC class I molecules by the MIR proteins.

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Acknowledgements

I am grateful to Nadine Jarousse for discussions and insights, as well as Brian Sullivan for editorial assistance. The laboratory is supported by grants from the National Cancer Institute, the National Institute of Allergy and Infectious diseases and the Pew Scholars Program in the Biological Sciences.

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  1. Department of Molecular and Cell Biology, University of California, Berkeley, 94720, California, USA

    Laurent Coscoy

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Glossary

Kaposi's sarcoma

A tumour of endothelial-cell origin that is found most frequently in immunosuppressed patients, particularly in HIV-infected individuals. KSHV has been implicated as a co-factor in the formation of Kaposi's sarcoma.

Gammaherpesviruses

One of the three subtypes of herpesviruses. Gammaherpesviruses are lymphotropic and several such viruses are known to have cellular transforming and oncogenic properties.

MicroRNAs

(miRNAs). Small, RNA molecules that regulate the expression of genes by binding to the 3′-untranslated regions (3′-UTR) of specific mRNAs.

Glomerulonephritis

An inflammation of the kidney glomeruli that can result in destruction of the glomeruli and renal failure.

Neoplasm

New or abnormal growth of tissue that might be benign or cancerous.

Angiogenesis

The process of the development of new blood vessels from existing blood vessels. It is frequently associated with tumour development and inflammation.

Plasma cells

Non-dividing, terminally differentiated, immunoglobulin-secreting cells of the B-cell lineage.

C3 and C5 convertases

Proteins that are activated by all three pathways of the complement system (the classical, lectin and alternative pathways) and generate the main effector molecules of this system.

p300

P300 (and CBP) are scaffolding proteins that interact with interferon (IFN) regulatory factors (IRFs) and other transcription factors promoting the recruitment of the RNA polymerase holoenzyme and allowing transcriptional activation of the IFN genes. Additionally, p300 and CBP have a histone acetyltransferase (HAT) activity, which endows these proteins with the capacity to influence chromatin activity by modulating nucleosomal histones.

Ubiquitylation

The attachment of the small protein ubiquitin to lysine residues that are present in other proteins. This tags these proteins for rapid cellular degradation. Protein ubiquitylation occurs in three enzymatic steps requiring a ubiquitin-activating enzyme (E1), a ubiquitin-conjugating enzyme (E2), and ubiquitin ligase (E3), which catalyses the ligation of an isopeptide bond between the carboxy-terminal domain of ubiquitin and an amino group belonging to a lysine residue of the target protein.

E3 ubiquitin ligase

Ubiquitin ligases recruit ubiquitin-conjugating enzymes, which attach the small polypeptide ubiquitin to proteins. The polyubiquitylated proteins are then subjected to proteasomal degradation. Polyubiquitylation, followed by proteasomal degradation, is one of the cellular mechanisms to eliminate proteins.

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Coscoy, L. Immune evasion by Kaposi's sarcoma-associated herpesvirus. Nat Rev Immunol 7, 391–401 (2007). https://doi.org/10.1038/nri2076

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