Kaposi's sarcoma-associated herpesvirus mitochondrial K7 protein targets a cellular calcium-modulating cyclophilin ligand to modulate intracellular calcium concentration and inhibit apoptosis

Pinghui Feng, Junsoo Park, Bok S. Lee, Sun H. Lee, Richard J Bram, Jae U. Jung

Research output: Contribution to journalArticle

84 Citations (Scopus)

Abstract

On viral infection, infected cells can become the target of host immune responses or can go through a programmed cell death process, called apoptosis, as a defense mechanism to limit the ability of the virus to replicate. To prevent this, viruses have evolved elaborate mechanisms to subvert the apoptotic process. Here, we report the identification of a novel antiapoptotic K7 protein of Kaposi's sarcoma-associated herpesvirus (KSHV) which expresses during lytic replication. The KSHV K7 gene encodes a small mitochondrial membrane protein, and its expression efficiently inhibits apoptosis induced by a variety of apoptogenic agents. The yeast two-hybrid screen has demonstrated that K7 targets cellular calcium-modulating cyclophilin ligand (CAML), a protein that regulates the intracellular Ca2+ concentration. Similar to CAML, K7 expression significantly enhances the kinetics and amplitudes of the increase in intracellular Ca2+ concentration on apoptotic stimulus. Mutational analysis showed that K7 interaction with CAML is required for its function in the inhibition of apoptosis. This indicates that K7 targets cellular CAML to increase the cytosolic Ca2+ response, which consequently protects cells from mitochondrial damage and apoptosis. This is a novel viral antiapoptosis strategy where the KSHV mitochondrial K7 protein targets a cellular Ca2+-modulating protein to confer resistance to apoptosis, which allows completion of the viral lytic replication and, eventually, maintenance of persistent infection in infected host.

Original languageEnglish (US)
Pages (from-to)11491-11504
Number of pages14
JournalJournal of Virology
Volume76
Issue number22
DOIs
StatePublished - Nov 2002
Externally publishedYes

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Human herpesvirus 8
cyclophilins
Cyclophilins
apoptosis
Apoptosis
Ligands
Calcium
calcium
proteins
Viruses
Human Herpesvirus 8
Mitochondrial Proteins
Mitochondrial Membranes
Virus Diseases
Membrane Proteins
Proteins
Cell Death
viruses
Yeasts
Maintenance

ASJC Scopus subject areas

  • Immunology

Cite this

Kaposi's sarcoma-associated herpesvirus mitochondrial K7 protein targets a cellular calcium-modulating cyclophilin ligand to modulate intracellular calcium concentration and inhibit apoptosis. / Feng, Pinghui; Park, Junsoo; Lee, Bok S.; Lee, Sun H.; Bram, Richard J; Jung, Jae U.

In: Journal of Virology, Vol. 76, No. 22, 11.2002, p. 11491-11504.

Research output: Contribution to journalArticle

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