Immune-mediated disease pathogenesis in respiratory syncytial virus infection

Graham, Barney S.; Johnson, Teresa R.; Peebles, R. Stokes

doi:10.1016/s0162-3109(00)00233-2

Cited by 113 publications

(89 citation statements)

References 55 publications

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“…Eosinophilia was dependent on the presence of IL-5 and CD4 ϩ T cells. In contrast, vaccination with vaccinia virus-expressed F protein (17,40) or with natural F protein mixed with an appropriate adjuvant (22) did not prime for eosinophilia. Recently it was reported that PBMC from most human volunteers readily recognized epitopes located within the central ectodomain encompassed by amino acids 149 to 200 of G protein (20).…”

mentioning

confidence: 80%

“…It is critical, however, that subunit vaccines do not elicit adaptive immune responses dominated by type 2 T cells. The exacerbated disease observed in RSV-naïve human infants to whom formalin-inactivated vaccines were administered (31,34) was associated with unbalanced type 2 T-cell responses (17,32). Asthma is associated with type 2 T cells and atopy (36).…”

Section: Discussionmentioning

confidence: 99%

“…Findings from several laboratories have established that immunization with highly purified native or vaccinia virus-expressed recombinant G pro-tein primed naïve BALB/c mice for pulmonary eosinophilia upon subsequent challenge with infectious RSV (17,40). Eosinophilia was dependent on the presence of IL-5 and CD4 ϩ T cells.…”

mentioning

confidence: 99%

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Characterization of Recombinant Respiratory Syncytial Viruses with the Region Responsible for Type 2 T-Cell Responses and Pulmonary Eosinophilia Deleted from the Attachment (G) Protein

Elliott¹,

Pryharski²,

et al. 2004

J Virol

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It is essential that preventative vaccines for respiratory syncytial virus (RSV) elicit balanced T-cell responses. Immune responses dominated by type 2 T cells against RSV antigens are believed to cause exaggerated respiratory tract disease and may also contribute to unwanted inflammation in the airways that predisposes infants to wheeze through adolescence. Here we report on the construction and characterization of recombinant RSV (rRSV) strains with amino acids 151 to 221 or 178 to 219 of the attachment (G) glycoprotein deleted (rA2cp⌬G150-222 or rA2cp⌬G177-220, respectively). The central ectodomain was chosen for modification because a peptide spanning amino acids 149 to 200 of G protein has recently been shown to prime several strains of naïve inbred mice for polarized type 2 T-cell responses, and peripheral blood T cells from most human donors recognize epitopes within this region. Quantitative PCR demonstrated that synthesis of nascent rRSV genomes in human lung epithelial cell lines was similar to that for the parent virus (cp-RSV). Plaque assays further indicated that rRSV replication was not sensitive to 37°C, but pinpoint morphology was observed at 39°C. Both rRSV strains replicated in the respiratory tracts of BALB/c mice and elicited serum neutralization and anti-F-protein immunoglobulin G titers that were equivalent to those elicited by cp-RSV and contributed to a 3.9-log 10 -unit reduction in RSV A2 levels 4 days after challenge. Importantly, pulmonary eosinophilia was significantly diminished in BALB/c mice primed with native G protein and challenged with either rA2cp⌬G150-222 or rA2cp⌬G177-220. These findings are important for the development of attenuated RSV vaccines.

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confidence: 80%

Section: Discussionmentioning

confidence: 99%

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Characterization of Recombinant Respiratory Syncytial Viruses with the Region Responsible for Type 2 T-Cell Responses and Pulmonary Eosinophilia Deleted from the Attachment (G) Protein

Elliott¹,

Pryharski²,

et al. 2004

J Virol

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“…Several precedents exist for vaccines to shift the host-pathogen interaction in harmful ways upon subsequent exposure to live virus (26)(27)(28)(29), including examples of vaccinemediated enhancement of lentivirus infections (30)(31)(32). Because lentiviral vaccine-mediated enhancement does not always involve enhancing antibodies (31), a mechanism of lymphocyte activation-mediated enhancement of virus replication has been proposed (33); data consistent with such a mechanism were reported in one feline immunodeficiency virus (FIV) vaccine study (34).…”

Section: Discussionmentioning

confidence: 99%

Enhanced SIV replication and accelerated progression to AIDS in macaques primed to mount a CD4 T cell response to the SIV envelope protein

Staprans

Barry

Silvestri

et al. 2004

Proc. Natl. Acad. Sci. U.S.A.

130

113

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Given the dual role of CD4 T cells as both immune effectors and targets for HIV infection, the balance of CD4 versus CD8 T cellmediated responses induced by candidate AIDS vaccines may be critical in determining postvaccination infection outcomes. An attenuated recombinant varicella-zoster virus vaccine expressing the simian immunodeficiency virus (SIV) envelope (Env) elicited nonneutralizing Env-binding antibodies and little if any cytotoxic T lymphocyte responses in rhesus macaques (Macaca mulatta). After challenge with SIV, Env vaccinees manifested increased levels of SIV replication, more rapid CD4 depletion, and accelerated progression to AIDS compared with controls. Enhanced SIV replication correlated with increased CD4 T cell proliferation soon after SIV challenge, apparently the result of an anamnestic response to SIV antigens. Thus activation of virusspecific CD4 T cells at the time of exposure to a CD4 T cell-tropic lentivirus, in the absence of an effective CD8 response, may enhance virus replication and disease. These data suggest suggest that candidate AIDS vaccines may not simply be either efficacious or neutral; they may also have the potential to be harmful.

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“…The most abundant cytokine in clinical specimens from RSVinfected children is IFN-␥, and most RSV infections likely resolve via a typical antiviral Th-1-type response (2). In BALB/c mice, RSV A2 strain infection causes an increase in the number of IFN-␥-producing NK cells in bronchoalveolar lavage fluid (BALF) that precedes the BALF appearance of abundant IFN-␥-producing CD8 cells and cytotoxic T lymphocytes (CTLs) (5)(6)(7). Both CD4 ϩ and CD8 ϩ T cells exacerbate RSV-induced illness and contribute to virus clearance in primary infection of BALB/c mice (8).…”

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confidence: 99%

Differential Regulation of GM1 and Asialo-GM1 Expression by T Cells and Natural Killer (NK) Cells in Respiratory Syncytial Virus Infection

et al. 2008

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We previously reported that respiratory syncytial virus (RSV) infection increases lung CD8 ϩ T cell GM1 expression. The related lipid asialo-GM1 (ASGM1) is expressed by T cells in viral infection and by natural killer (NK) cells. The in vivo co-expression of GM1 and ASGM1 by immune cells is not defined. Here we analyzed lung lymphocyte GM1 and ASGM1 expression in RSV-infected mice. GM1 and ASGM1 were coordinately upregulated by activated CD8 ϩ T cells in RSV-infected BALB/c and C57BL/6 mice. In contrast, RSV infection had no effect on constitutively high NK cell GM1 expression, while increasing NK cell ASGM1 expression. GM1 and ASGM1 co-localized in lipid raft structures in NK and CD8 ϩ T cells sorted from the lungs of RSV-infected mice. Anti-ASGM1 Ab treatment of RSV-infected BALB/c mice depleted GM1/ASGM1-expressing NK cells and GM1/ASGM1-expressing T cells, reduced lung IFN-␥ levels, increased viral load, delayed viral clearance, and reduced illness. STAT1 Ϫ/Ϫ mice are more susceptible to RSV replication and disease than wild-type mice. In RSV-infected STAT1 Ϫ/Ϫ mice, anti-ASGM1 Ab altered cytokine levels, but in contrast to BALB/c mice, antibody treatment had no effect on viral load or illness. Taken together, GM1 and ASGM1 expression are differentially regulated by T and NK cells in RSV infection. Also, GM1/ASGM1-expressing cells are important for control of RSV in BALB/c mice, whereas STAT1 Ϫ/Ϫ mice clear RSV by an alternative pathway. 327

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Immune-mediated disease pathogenesis in respiratory syncytial virus infection

Cited by 113 publications

References 55 publications

Characterization of Recombinant Respiratory Syncytial Viruses with the Region Responsible for Type 2 T-Cell Responses and Pulmonary Eosinophilia Deleted from the Attachment (G) Protein

Characterization of Recombinant Respiratory Syncytial Viruses with the Region Responsible for Type 2 T-Cell Responses and Pulmonary Eosinophilia Deleted from the Attachment (G) Protein

Enhanced SIV replication and accelerated progression to AIDS in macaques primed to mount a CD4 T cell response to the SIV envelope protein

Differential Regulation of GM1 and Asialo-GM1 Expression by T Cells and Natural Killer (NK) Cells in Respiratory Syncytial Virus Infection

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