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Viruses 2018, 10(9), 500; https://doi.org/10.3390/v10090500

Large-Scale Screening of HCMV-Seropositive Blood Donors Indicates that HCMV Effectively Escapes from Antibodies by Cell-Associated Spread

1
Institute for Virology, Ulm University Medical Center, 89081 Ulm, Germany
2
Institute for Transfusion Medicine, Ulm University Medical Center, 89081 Ulm, Germany
3
Institute for Clinical Transfusion Medicine and Immunogenetics Ulm, German Red Cross Blood Transfusion Service Baden-Württemberg–Hessen and Ulm University Medical Center, 89081 Ulm, Germany
4
Institute for Virology, University Hospital Essen, University of Duisburg-Essen, 45147 Essen, Germany
5
Division of Infection and Immunity, Cardiff University School of Medicine, Cardiff CF14 4XN, UK
*
Author to whom correspondence should be addressed.
Received: 17 August 2018 / Revised: 7 September 2018 / Accepted: 12 September 2018 / Published: 14 September 2018
(This article belongs to the Section Animal Viruses)
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Abstract

Immunoglobulins are only moderately effective for the treatment of human cytomegalovirus (HCMV) infections, possibly due to ineffectiveness against cell-associated virus spread. To overcome this limitation, we aimed to identify individuals with exceptional antibodies in their plasma that can efficiently block the cell-associated spread of HCMV. A Gaussia luciferase-secreting mutant of the cell-associated HCMV strain Merlin was generated, and luciferase activity evaluated as a readout for the extent of cell-associated focal spread. This reporter virus-based assay was then applied to screen plasma samples from 8400 HCMV-seropositive individuals for their inhibitory effect, including direct-acting antiviral drugs as positive controls. None of the plasmas reduced virus spread to the level of these controls. Even the top-scoring samples that partially reduced luciferase activity in the screening assay failed to inhibit focal growth when reevaluated with a more accurate, immunofluorescence-based assay. Selected sera with high neutralizing capacity against free viruses were analyzed separately, and none of them prevented the focal spread of three recent clinical HCMV isolates nor reduced the number of particles transmitted, as demonstrated with a fluorescent Merlin mutant. We concluded that donors with cell-to-cell-spread-inhibiting plasma are nonexistent or extremely rare, emphasizing cell-associated spread as a highly efficient immune escape mechanism of HCMV. View Full-Text
Keywords: cytomegalovirus; antibodies; cell-associated spread; immune evasion cytomegalovirus; antibodies; cell-associated spread; immune evasion
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Falk, J.J.; Winkelmann, M.; Laib Sampaio, K.; Paal, C.; Schrezenmeier, H.; Alt, M.; Stanton, R.; Krawczyk, A.; Lotfi, R.; Sinzger, C. Large-Scale Screening of HCMV-Seropositive Blood Donors Indicates that HCMV Effectively Escapes from Antibodies by Cell-Associated Spread. Viruses 2018, 10, 500.

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