Identification of Deletion Mutant Respiratory Syncytial Virus Strains Lacking Most of the G Protein in Immunocompromised Children with Pneumonia in South Africa

Venter, Marietjie; Niekerk, Stephanie van; Rakgantso, Andronica; Bent, Nicola

doi:10.1128/jvi.00674-11

Cited by 10 publications

(10 citation statements)

References 24 publications

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“…Similarly, while a number of truncated G proteins have been observed in RSV-B in vivo (29), we are unaware of reports of truncated G proteins in RSV-A in vivo. Studies of RSV escape from antibody-mediated selection have shown that premature stop codons in the C-terminal region can lead to antibody escape in cell culture (11).…”

Section: Resultsmentioning

confidence: 94%

Within-Host Whole-Genome Deep Sequencing and Diversity Analysis of Human Respiratory Syncytial Virus Infection Reveals Dynamics of Genomic Diversity in the Absence and Presence of Immune Pressure

Grad

Newman

Zody

et al. 2014

J Virol

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Human respiratory syncytial virus (RSV) is the leading cause of lower respiratory tract disease in infants and young children and an important respiratory pathogen in the elderly and immunocompromised. While population-wide molecular epidemiology studies have shown multiple cocirculating RSV genotypes and revealed antigenic and genetic change over successive seasons, little is known about the extent of viral diversity over the course of an individual infection, the origins of novel variants, or the effect of immune pressure on viral diversity and potential immune-escape mutations. To investigate viral population diversity in the presence and absence of selective immune pressures, we studied whole-genome deep sequencing of RSV in upper airway samples from an infant with severe combined immune deficiency syndrome and persistent RSV infection. The infection continued over several months before and after bone marrow transplant (BMT) from his RSV-immune father. RSV diversity was characterized in 26 samples obtained over 78 days. Diversity increased after engraftment, as defined by T-cell presence, and populations reflected variation mostly within the G protein, the major surface antigen. Minority populations with known palivizumab resistance mutations emerged after its administration. The viral population appeared to diversify in response to selective pressures, showing a statistically significant growth in diversity in the presence of pressure from immunity. Defining escape mutations and their dynamics will be useful in the design and application of novel therapeutics and vaccines. These data can contribute to future studies of the relationship between within-host and population-wide RSV phylodynamics. IMPORTANCEHuman RSV is an important cause of respiratory disease in infants, the elderly, and the immunocompromised. RSV circulating in a community appears to change season by season, but the amount of diversity generated during an individual infection and the impact of immunity on this viral diversity has been unclear. To address this question, we described within-host RSV diversity by whole-genome deep sequencing in a unique clinical case of an RSV-infected infant with severe combined immunodeficiency and effectively no adaptive immunity who then gained adaptive immunity after undergoing bone marrow transplantation. We found that viral diversity increased in the presence of adaptive immunity and was primarily within the G protein, the major surface antigen. These data will be useful in designing RSV treatments and vaccines and to help understand the relationship between the dynamics of viral diversification within individual hosts and the viral populations circulating in a community.H uman respiratory syncytial virus (RSV) is the leading cause of severe viral respiratory disease in infants and young children (1) and is a significant cause of morbidity and mortality in the elderly (2) and immunocompromised (3, 4). Reinfection can take place throughout life, although in older children and healthy adults infect...

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Section: Resultsmentioning

confidence: 94%

Within-Host Whole-Genome Deep Sequencing and Diversity Analysis of Human Respiratory Syncytial Virus Infection Reveals Dynamics of Genomic Diversity in the Absence and Presence of Immune Pressure

Grad

Newman

Zody

et al. 2014

J Virol

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“…A live-attenuated RSV vaccine candidate lacking most of the SH and G genes due to spontaneous deletions during passage in vitro appeared to be competent for replication in children, although it was highly restricted (Karron et al 1997a). RSV isolates have been found, from infants exposed to or infected with human immunodeficiency virus, with deletions spanning most of the G ectodomain, indicating that loss of most of G can occur in nature in some situations (Venter et al 2011). Thus, G is a malleable, variable protein that is absolutely not essential for replication.…”

Section: Proteinsmentioning

confidence: 99%

“…Virus passaged in vitro occasionally can acquire inserts of one (usually) or more U residues (negative sense) into the U tract at the end of GE signals or into untranslated sequence. Spontaneous deletion of the G and SH genes has been noted in vitro, and deletion of most of the G gene has been noted in vivo (Venter et al 2011). Two different spontaneous intragenic duplications of a segment of the G gene have been documented in nature (Eshaghi et al 2012), and in one case the resulting virus has spread worldwide and continued to evolve.…”

Section: Spontaneous Mutationsmentioning

confidence: 99%

Respiratory Syncytial Virus: Virology, Reverse Genetics, and Pathogenesis of Disease

Collins

Fearns

Graham

2013

Current Topics in Microbiology and Immunology

232

263

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Human respiratory syncytial virus (RSV) is an enveloped, nonsegmented negative-strand RNA virus of family Paramyxoviridae. RSV is the most complex member of the family in terms of the number of genes and proteins. It is also relatively divergent and distinct from the prototype members of the family. In the past 30 years, we have seen a tremendous increase in our understanding of the molecular biology of RSV based on a succession of advances involving molecular cloning, reverse genetics, and detailed studies of protein function and structure. Much remains to be learned. RSV disease is complex and variable, and the host and viral factors that determine tropism and disease are poorly understood. RSV is notable for a historic vaccine failure in the 1960s involving a formalin-inactivated vaccine that primed for enhanced disease in RSV naïve recipients. Live vaccine candidates have been shown to be free of this complication. However, development of subunit or other protein-based vaccines for pediatric use is hampered by the possibility of enhanced disease and the difficulty of reliably demonstrating its absence in preclinical studies.

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“…Many studies have confirmed that the premature stop codons affect the antigenicity of the G protein without modifying its entire function or its role in infectivity. Truncated genes have been described in both A subtypes [16] and with greater frequency in B subtype viruses [25], evidencing that this mechanism is important for generating genetic and antigenic diversity [4,26] and contributing to shaping the immune response in a defined population when changing the selective pressure on each subtype. For example, this stop codon apparition was used by the influenza A virus, which modified the length of NS1 without affecting its function [27] in a similar way to that used by RSV.…”

Section: Discussionmentioning

confidence: 99%

Description of respiratory syncytial virus genotypes circulating in Colombia

Ávila

Calvo

Barbosa

et al. 2018

J Infect Dev Ctries

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Introduction: Respiratory syncytial virus (RSV) is the most common cause of acute respiratory infections in children younger than two years but also produces infection in older children and even reinfection in people of any age, a characteristic related to the existence of different infecting subtypes and genotypes. Although Colombia has established the surveillance of classical respiratory viruses, there is no information about the RSV genotypes circulating in Colombian patients. Methodology: A subgroup of 227 previously RSV positive respiratory secretion samples were taken from a nationwide surveillance study, amplified and sequenced to define the circulation pattern of RSV subtypes and genotypes during 2000-2009 period in Colombia. Results. RSV exhibited seasonal behavior with an A subtype more prevalent. Both RSV subtypes had low nucleotide variability. During the study period, the GA2 and GA5 genotypes from RSV subtype A and the BA genotype from RSV subtype B were found. Conclusion. In this report, for the first time RSV genotypes circulating in Colombia were described, this information adds valuable information about virus epidemiology helping to understand the RSV epidemic and prepare our country for the introduction of new vaccines.

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Identification of Deletion Mutant Respiratory Syncytial Virus Strains Lacking Most of the G Protein in Immunocompromised Children with Pneumonia in South Africa

Abstract: Respiratory syncytial virus (RSV)G

Cited by 10 publications

References 24 publications

Within-Host Whole-Genome Deep Sequencing and Diversity Analysis of Human Respiratory Syncytial Virus Infection Reveals Dynamics of Genomic Diversity in the Absence and Presence of Immune Pressure

Within-Host Whole-Genome Deep Sequencing and Diversity Analysis of Human Respiratory Syncytial Virus Infection Reveals Dynamics of Genomic Diversity in the Absence and Presence of Immune Pressure

Respiratory Syncytial Virus: Virology, Reverse Genetics, and Pathogenesis of Disease

Description of respiratory syncytial virus genotypes circulating in Colombia

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