Research for Cytomegalovirus Mutations Associated With Resistance to Antivirals in Kidney Transplant Receptors

Author:

Sant’ Anna Carla de Castro12ORCID,Migone Silvia Regina da Cruz1,Rocha Carlos Alberto Machado da3,Mello Júnior Fernando Augusto Rodrigues1,Seabra Aline Damasceno1,Pontes Thaís Brilhante1,Rodrigues João Marildo1,Soares Salomé Aparecida1,Rego Viviane de Paiva1,Figueira Joana Paula1,Rodrigues Ana Paula Monteiro1,Burbano Rommel Mario Rodriguez12

Affiliation:

1. Molecular Biology Laboratory, Ophir Loyola Hospital, Belém, Brazil

2. Nucleus of Research in Oncology, Hospital Universitário João de Barros Barreto, Federal University of Pará, Belém, Brazil

3. Department of Biology and Health Sciences, Federal Institute of Pará, Belém, Brazil

Abstract

Cytomegalovirus (CMV) mutations associated with antiviral resistance have become a major problem related to high mortality in kidney transplant patients. The aim of the study was to investigate mutations in the CMV genes UL97 and UL54 associated with antiviral resistance. A retrospective observational cohort study was carried out at Hospital Ophir Loyola (HOL), a reference in Kidney Transplantation. A total of 81 patients who underwent kidney transplantation were followed up between 2016 and 2018 were monitored for CMV viral load by performing qPCR. Sanger sequencing was performed on 66 patients. All CMV-positive kidney transplant recipients were included. Mutations were observed in 15 samples (22.72%) from patients. Most cases involved UL97 mutations. Mutation in UL54 without mutation in UL97 was detected in only 2 cases. Resistance mutations in UL97 were identified, such as M460V, L595S, H520Q, two co-mutations D465R + Del524 and A594P + D413A and a 3 codon deletion (del598-601). The search for mutations in the CMV genes identified mutations that confer resistance to conventional antivirals, such as ganciclovir and cidofovir, used in the treatment of these patients. Confirmation of the association with increased CMV viral load in transplanted patients, due to mutation in resistance genes, requires phenotypic analysis for confirmation purposes. These were the first findings in patients in northern Brazil that we know of.

Funder

Conselho Nacional de Desenvolvimento Científico e Tecnológico

Publisher

SAGE Publications

Subject

Transplantation,Cell Biology,Biomedical Engineering

Reference15 articles.

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