TAILIEUCHUNG - Báo cáo khoa học: The human cytomegalovirus-encoded chemokine receptor US28 induces caspase-dependent apoptosis

Viral subversion of apoptosis regulation plays an important role in the outcome of host⁄virus interactions. Although human cytomegalovirus (HCMV) encodes several immediate early (IE) antiapoptotic proteins (IE1, IE2, vMIA and vICA), no proapoptotic HCMV protein has yet been iden-tified. Here we show that US28, a functional IE HCMV-encoded chemo-kine receptor, which may be involved in both viral dissemination and immune evasion, constitutively induces apoptosis in several cell types. | ềFEBS Journal The human cytomegalovirus-encoded chemokine receptor US28 induces caspase-dependent apoptosis 111 ri ZM p IQQ Ixz-vff1 2 Pa I o f acQKAca2 q mo 1111 Eado I A I nz-vI I n 1 Pa t iz x p zt Ĩ c e zt r3 Olivier Pleskoil raUla CaoalUoa LaUlellUe veilieuil raUcla AIIIUUII Panick Deissei Martine Smit2 Rob Leurs2 Pascal Schneider4 Susan Michelson5 and Jean Claude Ameisen1 1 EMI-U 9922 INSERM Universite Paris 7 France 2 Leiden Amsterdam Center for Drug Research Division of MedicinalChemistry the Netherlands 3 Department of MedicalMicrobiology University Hospitalof Maastricht the Netherlands 4 Institute of Biochemistry University of Lausanne Epalinges Switzerland 5 Unite d lmmunologie Virale Institut Pasteur Paris France Keywords apoptosis caspases chemokine receptor cytomegalovirus immediate early proteins Correspondence O. Pleskoff Leiden Amsterdam Center for Drug Research Division of Medicinal Chemistry Faculty of Chemistry De Boelelaan 1083 1081 HV Amsterdam the Netherlands Fax 31 20 444 7610 Tel 31 20 444 7579 E-mail P. Casarosa and L. Verneuilcontributed equally to this work Received 21 April2005 revised 17 June 2005 accepted 21 June 2005 doi Viral subversion of apoptosis regulation plays an important role in the outcome of host virus interactions. Although human cytomegalovirus HCMV encodes several immediate early IE antiapoptotic proteins IE1 IE2 vMIA and vICA no proapoptotic HCMV protein has yet been identified. Here we show that US28 a functional IE HCMV-encoded chemo-kine receptor which may be involved in both viral dissemination and immune evasion constitutively induces apoptosis in several cell types. In contrast none of nine human cellular chemokine receptors belonging to three different subfamilies induced any significant level of apoptosis. US28-induced cell death involves caspase 10 and caspase 8 activation but does not depend on the engagement of cell-surface death receptors of the .

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