Understanding the Epidemiology of Adenovirus and its Evolution in Patients with Viremia

Clinical Center

Investigators

Abstract

Detection of variants is important in understanding the epidemiology of viral infections and has been very significant in the COVID-19 pandemic. Persistent viral replication in immunocompromised patients is likely the result of profound lymphocyte defects due to B- and T-celldepleting therapies or underlying hematologic disease. Viral persistence in the setting of immunosuppression for viral evolution and emergence of variants, especially during treatment with convalescent plasma. We demonstrated a 497-nt deletion spanning the entire length of the ORF7b coding region and all but 2 amino acids of ORF8 in a patient persistently infected for 335 days with SARS-CoV-2. These findings provide insight into viral evolution in persistent infections that can have implications for emergence of viral variants. Adenovirus is a phylogenetically diverse pathogen and is divided into seven species A-G, there are currently over 80 known types and new adenovirus genotypes continue to evolve. In immunosuppressed especially in allogenic transplant recipients HAdV-A, -B, and -C are all associated with infections. The phylogeny of adenovirus is an evolving area of research and recombination and genetic drift have shown evolution of new adenovirus types. Recombination among capsid genes and selection of new sequences are factors responsible for genetic diversity. During prolonged infection especially in immunocompromised hosts, the potential for evolution of a viral pathogen is high. However, capturing the viral load and the genotypes at any given point during infection and tracking of evolution during infection can be difficult given the possibility of mixed genotypic variants. Additionally, there could be a possibility that the virome or microbiome of the patient could reflect the evolution of adenovirus over time. The plasma microbiome/virome could also be affecting the clinical course of these patients. These questions were addressed as follows: 1. We evaluated a robust method of DNA extraction and library preparation for shotgun metagenomic sequencing from archived plasma specimens that were low yield. We demonstrated that the library preparation and the metagenomic shotgun sequencing approach generated viral reads that correlated with the viral load quantitated using real-time PCR assays. We demonstrated that this approach was able to detect the microbiome of the patient (bacterial and viral pathogens were detected in plasma). 2. We are using bioinformatics algorithms to investigate mutations in the capsid proteins (eg. Hexon gene) in our patient population and also in each patient over time. We are also determining the major adenovirus types circulating in our cohort. 3. We plan to correlate these findings with clinical course of our patient population. We also intend to look into the presence of other viruses such as adeno associated viruses that may have an impact on the epidemiology of adenoviruses detected in our patient cohort. Publications generated during reporting period: PMID: 34940844 1. Veronique Nussenblatt, Allison E Roder, Sanchita Das, Emmie de Wit, Jung-Ho Youn, Stephanie Banakis, Alexandra Mushegian, Christopher Mederos, Wei Wang, Matthew Chung, Lizzette Prez-Prez, Tara Palmore, Jennifer N Brudno, James N Kochenderfer, Elodie Ghedin, Yearlong COVID-19 Infection Reveals Within-Host Evolution of SARS-CoV-2 in a Patient With B-Cell Depletion, The Journal of Infectious Diseases, Volume 225, Issue 7, 1 April 2022, Pages 11181123 PMID: 34198050 PMCID: PMC8213877 2. Totten AH, Youn JH, Roder A, Ghedin E, Palmore TN, Frank KM, Das S, Zelazny AM. Detection of SARS-CoV2 variants by Mesa Accula. J Clin Virol. 2021 Aug;141:104901.