Respiratory Syncytial Virus and Human Metapneumovirus Infection in Transplant Recipients

Renaud, Christian; Englund, Janet A.

doi:10.1007/978-3-319-28797-3_31

Cited by 1 publication

(1 citation statement)

References 127 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Prolonged shedding for >4 weeks has been documented in hospitalized infants. HCT patients with an impaired cellular immunity are at risk of extended viral shedding and high mortality ( Renaud and Englund 2016 ). Although viral load and duration of RSV shedding play an important role in disease outcome and transmission, a less understood dynamic is the inter-host and intra-host genetic diversity of the virus over time and under varying immune pressures.…”

Section: Introductionmentioning

confidence: 99%

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

Avadhanula,

Agustinho,

Menon

et al. 2023

Virus Evolution

View full text Add to dashboard Cite

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.

show abstract

Section: Introductionmentioning

confidence: 99%