Targeting the latent human cytomegalovirus reservoir with virus specific nanobodies

Timo W.M. De Groof, Elizabeth G. Elder, Raimond Heukers, Eleanor Y. Lim, Mark Wills, John H. Sinclair, Martine J. Smit

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Received Date: 15th April 20

Latent reservoirs of viral pathogens are significant barriers to eradication of these viruses. During latency, herpesviruses maintain their genome, with little gene expression, making latent infections refractory to current treatments targeting viral replication. In the case of human cytomegalovirus (HCMV), sporadic reactivation events are well controlled by the immune system. However, in immunocompromised or immunosuppressed individuals, HCMV reactivation often results in morbidity in solid organ and stem cell transplant patients. Clearance of the latent reservoir could lower the incidence and severity of HCMV-associated disease. Here, we develop a virus specific nanobody (VUN100b) that partially inhibits signaling of the viral receptor US28. VUN100b treatment partially reverses latency without fully reactivating the virus. Moreover, VUN100b treatment drives recognition and killing of latently infected monocytes by autologous cytotoxic T lymphocytes from HCMV-seropositive individuals. This study shows the potential of VUN100b as a therapy to clear the HCMV latent reservoir of transplant patients.

Read in full at bioRxiv.

This is an abstract of a preprint hosted on an independent third party site. It has not been peer reviewed but is currently under consideration at Nature Communications.

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