Tegument Protein pp150 Sequence-Specific Peptide Blocks Cytomegalovirus Infection

Human cytomegalovirus (HCMV) tegument protein pp150 is essential for the completion of the final steps in virion maturation. Earlier studies indicated that three pp150nt (N-terminal one-third of pp150) conformers cluster on each triplex (Tri1, Tri2A and Tri2B), and extend towards small capsid protei...

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Autores principales:	Dipanwita Mitra, Mohammad H. Hasan, John T. Bates, Gene L. Bidwell, Ritesh Tandon
Formato:	article
Lenguaje:	EN
Publicado:	MDPI AG 2021
Materias:	CMV herpesviruses peptide therapy tegument nuclear egress Microbiology QR1-502
Acceso en línea:	https://doaj.org/article/bb915d78c1114fd0b9b2e87d081861e6
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spelling	oai:doaj.org-article:bb915d78c1114fd0b9b2e87d081861e62021-11-25T19:14:02ZTegument Protein pp150 Sequence-Specific Peptide Blocks Cytomegalovirus Infection10.3390/v131122771999-4915https://doaj.org/article/bb915d78c1114fd0b9b2e87d081861e62021-11-01T00:00:00Zhttps://www.mdpi.com/1999-4915/13/11/2277https://doaj.org/toc/1999-4915Human cytomegalovirus (HCMV) tegument protein pp150 is essential for the completion of the final steps in virion maturation. Earlier studies indicated that three pp150nt (N-terminal one-third of pp150) conformers cluster on each triplex (Tri1, Tri2A and Tri2B), and extend towards small capsid proteins atop nearby major capsid proteins, forming a net-like layer of tegument densities that enmesh and stabilize HCMV capsids. Based on this atomic detail, we designed several peptides targeting pp150nt. Our data show significant reduction in virus growth upon treatment with one of these peptides (pep-CR2) with an IC<sub>50</sub> of 1.33 μM and no significant impact on cell viability. Based on 3D modeling, pep-CR2 specifically interferes with the pp150–capsid binding interface. Cells pre-treated with pep-CR2 and infected with HCMV sequester pp150 in the nucleus, indicating a mechanistic disruption of pp150 loading onto capsids and subsequent nuclear egress. Furthermore, pep-CR2 effectively inhibits mouse cytomegalovirus (MCMV) infection in cell culture, paving the way for future animal testing. Combined, these results indicate that CR2 of pp150 is amenable to targeting by a peptide inhibitor, and can be developed into an effective antiviral.Dipanwita MitraMohammad H. HasanJohn T. BatesGene L. BidwellRitesh TandonMDPI AGarticleCMVherpesvirusespeptide therapytegumentnuclear egressMicrobiologyQR1-502ENViruses, Vol 13, Iss 2277, p 2277 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	CMV herpesviruses peptide therapy tegument nuclear egress Microbiology QR1-502
spellingShingle	CMV herpesviruses peptide therapy tegument nuclear egress Microbiology QR1-502 Dipanwita Mitra Mohammad H. Hasan John T. Bates Gene L. Bidwell Ritesh Tandon Tegument Protein pp150 Sequence-Specific Peptide Blocks Cytomegalovirus Infection
description	Human cytomegalovirus (HCMV) tegument protein pp150 is essential for the completion of the final steps in virion maturation. Earlier studies indicated that three pp150nt (N-terminal one-third of pp150) conformers cluster on each triplex (Tri1, Tri2A and Tri2B), and extend towards small capsid proteins atop nearby major capsid proteins, forming a net-like layer of tegument densities that enmesh and stabilize HCMV capsids. Based on this atomic detail, we designed several peptides targeting pp150nt. Our data show significant reduction in virus growth upon treatment with one of these peptides (pep-CR2) with an IC<sub>50</sub> of 1.33 μM and no significant impact on cell viability. Based on 3D modeling, pep-CR2 specifically interferes with the pp150–capsid binding interface. Cells pre-treated with pep-CR2 and infected with HCMV sequester pp150 in the nucleus, indicating a mechanistic disruption of pp150 loading onto capsids and subsequent nuclear egress. Furthermore, pep-CR2 effectively inhibits mouse cytomegalovirus (MCMV) infection in cell culture, paving the way for future animal testing. Combined, these results indicate that CR2 of pp150 is amenable to targeting by a peptide inhibitor, and can be developed into an effective antiviral.
format	article
author	Dipanwita Mitra Mohammad H. Hasan John T. Bates Gene L. Bidwell Ritesh Tandon
author_facet	Dipanwita Mitra Mohammad H. Hasan John T. Bates Gene L. Bidwell Ritesh Tandon
author_sort	Dipanwita Mitra
title	Tegument Protein pp150 Sequence-Specific Peptide Blocks Cytomegalovirus Infection
title_short	Tegument Protein pp150 Sequence-Specific Peptide Blocks Cytomegalovirus Infection
title_full	Tegument Protein pp150 Sequence-Specific Peptide Blocks Cytomegalovirus Infection
title_fullStr	Tegument Protein pp150 Sequence-Specific Peptide Blocks Cytomegalovirus Infection
title_full_unstemmed	Tegument Protein pp150 Sequence-Specific Peptide Blocks Cytomegalovirus Infection
title_sort	tegument protein pp150 sequence-specific peptide blocks cytomegalovirus infection
publisher	MDPI AG
publishDate	2021
url	https://doaj.org/article/bb915d78c1114fd0b9b2e87d081861e6
work_keys_str_mv	AT dipanwitamitra tegumentproteinpp150sequencespecificpeptideblockscytomegalovirusinfection AT mohammadhhasan tegumentproteinpp150sequencespecificpeptideblockscytomegalovirusinfection AT johntbates tegumentproteinpp150sequencespecificpeptideblockscytomegalovirusinfection AT genelbidwell tegumentproteinpp150sequencespecificpeptideblockscytomegalovirusinfection AT riteshtandon tegumentproteinpp150sequencespecificpeptideblockscytomegalovirusinfection
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Tegument Protein pp150 Sequence-Specific Peptide Blocks Cytomegalovirus Infection

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