Inter and intra-host diversity of RSV in hematopoietic stem cell transplant adults with normal and delayed viral clearance

Abstract

Respiratory syncytial virus (RSV) infection in immunocompromised individuals often leads to prolonged illness, progression to severe lower respiratory tract infection and even death. How host immune environment of the Hematopoietic Stem Cell Transplant (HCT) adults can affect viral genetic variation during an acute infection is not understood well. In the present study, we performed whole genome sequencing of RSV/A or RSV/B from samples collected longitudinally from HCT adults with normal (<14 days) and delayed (≥14 days) RSV clearance who were enrolled in a Ribavirin trial. We determined the inter-host and intra-host genetic variation of RSV and the effect of mutations on putative glycosylation sites. The inter-host variation of RSV centered in the Attachment (G), Fusion (F) glycoprotein genes followed by polymerase (L) and matrix (M) genes. Interestingly, the overall genetic variation was constant between normal and delayed clearance groups for both RSV/A and RSV/B. Intra-host variation, primarily occurred in the G gene followed by non-structural protein (NS1), and L genes, however, gain or loss of stop codons, and frameshift mutations appeared only in the G gene and only in the delayed viral clearance group. Potential gain or loss of O-linked glycosylation sites in the G gene occurred both in RSV/A and RSV/B isolates. For RSV F gene, loss of N-linked glycosylation site occurred in three RSV/B isolates within an antigenic epitope. Both oral and aerosolized Ribavirin did not cause any mutations in the L gene. In summary, prolonged viral shedding and immune deficiency resulted in RSV variation, especially in structural mutations in the G gene, possibly associated with immune evasion. Therefore, sequencing and monitoring of RSV isolates from immunocompromised patients is crucial as they can create escape mutants that can impact the effectiveness of upcoming vaccines and treatments.

IAVCP (Influenza A Virus Consensus and Phylogeny): Automatic Identification of the Genomic Sequence of the Influenza A Virus from High-Throughput Sequencing Data

“…IRMA overcomes these shortcomings and is widely used in recent publications describing new IAV sequences [52][53][54]. However, the databases used in this tool cannot be updated by users.…”

“…For the consensus sequences of the new virus generation using the INSaFLU reference sequences, user-defined sequences should be used, eliminating the possibility of fully automated analysis. IRMA overcomes these shortcomings and is widely used in recent publications describing new IAV sequences [ 52 , 53 , 54 ]. However, the databases used in this tool cannot be updated by users.…”

Whole-Genome Sequencing and Genetic Diversity of Human Respiratory Syncytial Virus in Patients with Influenza-like Illness in Sicily (Italy) from 2017 to 2023

“…Although it is estimated that hRSV affects almost all children worldwide at least once within the first two years of life [ 2 ], the global burden of hRSV infections extends beyond very young children, remaining frequent at later ages also [ 3 , 4 ], including subjects with underlying medical conditions [ 5 , 6 ], the elderly [ 7 , 8 ] and immunocompromised individuals [ 9 ], who are increasingly being recognized as vulnerable populations at significant risk of severe infection and death.…”