Treatment of respiratory syncytial virus infection with recombinant interferon alfa-2a.

Sung, Rita Yn Tz; Yin, Jun; Oppenheimer, Stephen; Tam, John S.; Lau, Jyn

doi:10.1136/adc.69.4.440

Cited by 36 publications

(24 citation statements)

References 12 publications

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“…Unfortunately, the clinical trial showed that daily intramuscular injection of IFN-␣ into RSV-infected infants for three consecutive days did not change the overall clinical course, the duration of oxygen requirement, or viral shedding, although the treatment did induce a more rapid drop in the clinical score during the first 3 days (33). The difference between these human studies and our data in neonates may be explained by the different strategies that we employed.…”

Section: Discussioncontrasting

confidence: 54%

Limited Type I Interferons and Plasmacytoid Dendritic Cells during Neonatal Respiratory Syncytial Virus Infection Permit Immunopathogenesis upon Reinfection

Cormier

Shrestha

Saravia

et al. 2014

J Virol

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Respiratory syncytial virus (RSV) infection is the number one cause of bronchiolitis in infants IMPORTANCE Respiratory syncytial virus (RSV) is the most significant cause of lower respiratory tract infection in infancy worldwide.Despite the dire need, we have failed to produce efficacious RSV vaccines or therapeutics. Part of the reason for this failure is our lack of understanding of how RSV interacts with the infant immune system to suppress the development of protective immunity. In the study described in the present paper, we used a neonatal mouse model, which more closely mimics human infants, to study the role of the innate immune system, particularly type I interferons (IFNs) and plasmacytoid dendritic cells (pDCs), in the pathogenesis of RSV infection. RSV infection in neonates induced limited type I IFN and pDC responses. IFN-␣ treatment or adoptive transfer of adult pDCs capable of producing IFN-␣ prior to neonatal RSV infection decreased Th2-biased immunopathogenesis during reinfection. These data suggest that IFN-␣ is a promising target for future RSV vaccine design.

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Section: Discussioncontrasting

confidence: 54%

Limited Type I Interferons and Plasmacytoid Dendritic Cells during Neonatal Respiratory Syncytial Virus Infection Permit Immunopathogenesis upon Reinfection

Cormier

Shrestha

Saravia

et al. 2014

J Virol

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“…was added upon collection, were stored at Ϫ70°C and then shipped to the United States in the frozen state (Ϫ70°C). The culture methods for the detection of all viruses, including RSV, in clinical respiratory specimens were described previously (27). For detection of the viral antigen of RSV by IF, the cells from the clinical specimens were washed, concentrated, and spotted on slides.…”

Section: Methodsmentioning

confidence: 99%

“…For detection of the viral antigen of RSV by IF, the cells from the clinical specimens were washed, concentrated, and spotted on slides. The slides were then stained using IMAGEN (Dako Diagnostics, Ely, United Kingdom) and analyzed as described previously (27).…”

Section: Methodsmentioning

confidence: 99%

Simultaneous Detection, Subgrouping, and Quantitation of Respiratory Syncytial Virus A and B by Real-Time PCR

Hu¹,

et al. 2003

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Timely diagnosis of respiratory syncytial virus (RSV) infection is critical for appropriate treatment of lower respiratory infection in young children. To facilitate diagnosis, we developed a rapid, specific, and sensitive TaqMan Respiratory syncytial virus (RSV) is one of the major respiratory pathogens causing lower respiratory tract diseases in children (10,18,23). Based on genetic and antigenic variations in the structural proteins, RSV is classified into two subgroups, A and B (3, 24). At present, there is no vaccine available for prevention of the viral infection, although antiviral therapy is known to be effective in some patients (1, 2, 11). For appropriate treatment of RSV infection, it is crucial to have an accurate and timely diagnostic method for detection of the virus.A number of techniques are available for detection and identification of RSV, including cell culture, enzyme immunoassay (EIA), immunofluorescence (IF), and conventional reverse transcription (RT)-PCR (6,7,8,9,12,16,17,21,22,25). The classical cell culture method requires prompt inoculation of the labile virus and is a time-consuming process. In addition, the test has low sensitivity, detecting only 50 to 60% of RSV infections (17). More rapid immunoassays for the detection of RSV, such as EIA and IF, also have limitations in sensitivity and specificity. The accuracy of EIA, for example, is in the range of 57 to 98%, and that of IF varies from 65 to 92% (12). This wide variability in assay sensitivity and specificity may lead to inaccurate diagnosis of RSV infection, and consequently, the assays may be of limited value in patient care. Furthermore, such rapid immunoassays are rarely capable of differentiating RSV subgroups A and B, which may be associated with different disease severities (28).Conventional RT-PCR, which has recently been developed for the detection of RSV, is a more sensitive and specific diagnostic method that also allows for the subgrouping of the virus in a single reaction (6,7,8,9,17,25). However, it still requires time-consuming post-PCR analysis. Real-time RT-PCR, on the other hand, eliminates post-PCR processing (13). This is achieved by combining conventional RT-PCR with advanced fluorescence detection technology, which allows the fluorescence signals to be analyzed and recorded during PCR cycling. The advanced method also performs automatic sample analysis with enhanced sensitivity and specificity. In this report, we describe the development and application of a TaqManbased RT-PCR assay for simultaneous detection, subgrouping, and quantification of RSV A and B in clinical respiratory specimens. MATERIALS AND METHODSVirus stocks, plaque titration, and virus particle counts. RSV A2 (subgroup A) and 2B (subgroup B) were propagated in Vero cells. About 100 ml each of subgroup A and B virus stocks were prepared, and the stocks were stored in 0.5-ml aliquots for future use. For plaque titration of RSV stocks, confluent Vero cells in 24-well plates were inoculated with 100 l of a serial dilution of each virus at 37°...

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“…One study reported that intramuscular treatment of RSV-infected children with IFN-␣ did improve their clinical course after the second day of treatment (53). On the other hand, Chipps et al reported that children with bronchiolitis caused by RSV who were treated with intramuscular injection of IFN-␣ did not show significant difference in the clinical course, duration of oxygen requirement, or physical assessment compared to a placebo group.…”

mentioning

confidence: 95%

Activity and Regulation of Alpha Interferon in Respiratory Syncytial Virus and Human Metapneumovirus Experimental Infections

Guerrero-Plata¹,

Baron

Poast

et al. 2005

J Virol

113

142

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Respiratory syncytial virus (RSV) and human metapneumovirus (hMPV) cause a similar spectrum of respiratory infections in humans. Classified within the Paramyxoviridae family, Pneumovirinae subfamily, RSV and hMPV present a significant degree of divergence in genome constellation, organization, and protein sequences. RSV has been reported to be a poor inducer of alpha/beta interferons (IFN-␣/␤) and partially resistant to its antiviral activity. The nature of the innate immune response to hMPV is currently unknown. Herein, an experimental mouse model was used to investigate the interplay between RSV and hMPV infections and IFN-␣ in the airways. RSV-infected BALB/c mice treated intranasally with either poly-ICLC, a potent inducer of IFN-␣, or directly with recombinant IFN-␣ showed significantly reduced lung viral titers, inflammation, and clinical disease than untreated controls. However, RSV was significantly less sensitive to the antiviral activity of IFN-␣ than hMPV. Similarly, when the ability to directly induce IFN-␣ production was assessed, RSV was clearly a weaker inducer of IFN-␣ than hMPV, as shown by both kinetics and the absolute amount of IFN-␣ secreted into the bronchoalveolar lavage. To further investigate the putative inhibitory effect of these viruses on IFN-␣ production, mice were infected for 48 h prior to treatment with poly-ICLC or a specific Toll-like receptor 9 ligand, CpG oligodeoxynucleotides. Strikingly, both poly-ICLC-and CpG-mediated IFN-␣ production was abrogated by either RSV or MPV infection. These results suggest that a complex interplay between virus-specific and host-mediated responses regulates IFN-␣ in the lung during infection by members of the Pneumovirinae family.

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Treatment of respiratory syncytial virus infection with recombinant interferon alfa-2a.

Cited by 36 publications

References 12 publications

Limited Type I Interferons and Plasmacytoid Dendritic Cells during Neonatal Respiratory Syncytial Virus Infection Permit Immunopathogenesis upon Reinfection

Limited Type I Interferons and Plasmacytoid Dendritic Cells during Neonatal Respiratory Syncytial Virus Infection Permit Immunopathogenesis upon Reinfection

Simultaneous Detection, Subgrouping, and Quantitation of Respiratory Syncytial Virus A and B by Real-Time PCR

Activity and Regulation of Alpha Interferon in Respiratory Syncytial Virus and Human Metapneumovirus Experimental Infections

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