Anticytomegalovirus peptides point to new insights for CMV entry mechanisms and the limitations of in vitro screenings

Joseph W. Jackson, Trevor J. Hancock, Pranay Dogra, Ravi Patel, Ravit Arav-Boger, Angela D. Williams, Stephen J. Kennel, Jonathan S. Wall, Tim E. Sparer

Research output: Contribution to journalArticle

Abstract

Human cytomegalovirus (HCMV) is a ubiquitous betaherpesvirus that can cause severe disease following in utero exposure, during primary infection, or latent virus reactivation in immunocompromised populations. These complications lead to a 1- to 2-billion-dollar economic burden, making vaccine development and/or alternative treatments a high priority. Current treatments for HCMV include nucleoside analogues such as ganciclovir (GCV), foscarnet, and cidofovir. Recently, letermovir, a terminase complex inhibitor, was approved for prophylaxis after stem cell transplantation. These treatments have unwanted side effects, and HCMV is becoming resistant to them. Therefore, we sought to develop an alternative treatment that targets a different stage in viral infection. Currently, small antiviral peptides are being investigated as anti-influenza and anti-HIV treatments. We have developed heparan sulfate-binding peptides as tools for preventing CMV infections. These peptides are highly effective at stopping infection of fibroblasts with in vitro-derived HCMV and murine cytomegalovirus (MCMV). However, they do not prevent MCMV infection in vivo. Interestingly, these peptides inhibit infectivity of in vivo-derived CMVs, albeit not as well as tissue culture-grown CMVs. We further demonstrate that this class of heparan sulfate-binding peptides is incapable of inhibiting MCMV cellto- cell spread, which is independent of heparan sulfate usage. These data indicate that inhibition of CMV infection can be achieved using synthetic polybasic peptides, but cell-to-cell spread and in vivo-grown CMVs require further investigation to design appropriate anti-CMV peptides.

Original languageEnglish (US)
Article numbere00586-18
JournalmSphere
Volume4
Issue number1
DOIs
StatePublished - Jan 1 2019

Keywords

  • Antiviral peptides
  • Cytomegalovirus
  • Entry
  • HCMV
  • Heparan sulfate
  • MCMV

ASJC Scopus subject areas

  • Microbiology
  • Molecular Biology

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  • Cite this

    Jackson, J. W., Hancock, T. J., Dogra, P., Patel, R., Arav-Boger, R., Williams, A. D., Kennel, S. J., Wall, J. S., & Sparer, T. E. (2019). Anticytomegalovirus peptides point to new insights for CMV entry mechanisms and the limitations of in vitro screenings. mSphere, 4(1), [e00586-18]. https://doi.org/10.1128/mSphere.00586-18