Targeting the Latent Cytomegalovirus Reservoir with an Antiviral Fusion Toxin Protein

Overview

Journal Nat Commun

Specialty Biology

Date 2017 Feb 3

PMID 28148951

Citations 43

Authors

B A Krishna

K Spiess

E L Poole

B Lau

S Voigt

T N Kledal

M M Rosenkilde

J H Sinclair

Affiliations

Soon will be listed here.

Abstract

Reactivation of human cytomegalovirus (HCMV) in transplant recipients can cause life-threatening disease. Consequently, for transplant recipients, killing latently infected cells could have far-reaching clinical benefits. In vivo, myeloid cells and their progenitors are an important site of HCMV latency, and one viral gene expressed by latently infected myeloid cells is US28. This viral gene encodes a cell surface G protein-coupled receptor (GPCR) that binds chemokines, triggering its endocytosis. We show that the expression of US28 on the surface of latently infected cells allows monocytes and their progenitor CD34+ cells to be targeted and killed by F49A-FTP, a highly specific fusion toxin protein that binds this viral GPCR. As expected, this specific targeting of latently infected cells by F49A-FTP also robustly reduces virus reactivation in vitro. Consequently, such specific fusion toxin proteins could form the basis of a therapeutic strategy for eliminating latently infected cells before haematopoietic stem cell transplantation.

Citing Articles

CMV Retinitis in the Context of SARS-CoV-2 Infection: A Case Study and Comprehensive Review of Viral Interactions.

Stoicescu E, Ghenciu L, Iacob R, Ardelean A, Daescu E, Hategan O Pathogens. 2024; 13(11).

PMID: 39599491 PMC: 11597558. DOI: 10.3390/pathogens13110938.

Virus-Specific Nanobody-Chimeras Degrade the Human Cytomegalovirus US28 Protein in CD34+ Cells.

Poole E, Schmitt J, Graham S, Kelly B, Sinclair J Pathogens. 2024; 13(10).

PMID: 39452693 PMC: 11510245. DOI: 10.3390/pathogens13100821.

Delivery of US28 by incoming HCMV particles rapidly attenuates Akt activity to suppress HCMV lytic replication in monocytes.

Mahmud J, Geiler B, Biswas J, Miller M, Myers J, Matthews S Sci Signal. 2024; 17(851):eadn8727.

PMID: 39190708 PMC: 11460310. DOI: 10.1126/scisignal.adn8727.

Therapeutic targeting of HCMV-encoded chemokine receptor US28: Progress and challenges.

Berg C, Rosenkilde M Front Immunol. 2023; 14:1135280.

PMID: 36860859 PMC: 9968965. DOI: 10.3389/fimmu.2023.1135280.

Cytomegalovirus US28 regulates cellular EphA2 to maintain viral latency.

Wass A, Krishna B, Herring L, Gilbert T, Nukui M, Groves I Sci Adv. 2022; 8(43):eadd1168.

PMID: 36288299 PMC: 9604534. DOI: 10.1126/sciadv.add1168.

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