Human cytomegalovirus (HCMV) establishes lifelong latent infections that remain asymptomatic in healthy individuals due to immune control. However, HCMV poses a serious threat to immunocompromised patients, particularly transplant recipients. In transplantation, latent HCMV in donated organs is a major risk factor for reactivation in immunosuppressed recipients. Despite CMV prophylaxis, reactivation occurs in up to 40% of patients, increasing the risk of organ rejection and mortality. As current antiviral therapies target only the lytic phase of HCMV, latent infections remain unresolved which then act as reservoirs for subsequent virus reactivation. Here, we describe the use of a novel antiviral drug candidate, SYN002, which targets the viral US28 protein, a cell surface protein expressed during all phases of the viral lifecycle, including latency. SYN002 is a recombinant immunotoxin targeting US28 on the surface of HCMV-infected cells, internalizing with the receptor and inducing apoptosis in infected cells. We show that delivery of SYN002 into human kidneys, using ex vivo perfusion, results in a substantial and clinically relevant reduction of virus shedding from the donor kidney. Such a strategy could allow the targeted removal of HCMV from donor kidneys prior to transplantation and the prevention of HCMVmediated disease in kidney transplant recipients.
Emma Poole (Wed,) studied this question.