Antigen processing and presentation of human rhinovirus to CD4 T cells is facilitated by binding to cellular receptors for virus

Hastings, Gillian Z.; Francis, Michael J.; Rowlands, David J.; Chain, Benjamin M.

doi:10.1002/eji.1830230623

Cited by 9 publications

(9 citation statements)

References 21 publications

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“…Minor-group viruses are more effective than major-group viruses in stimulating T-cell responses in vitro (25). We hypothesized that as a consequence, minor-group viruses would induce stronger antibody responses and thereby experience higher rates of amino acid substitutions at sites exposed to the immune system.…”

Section: Figmentioning

confidence: 99%

“…ICAM-1 is an important cell adhesion molecule that facilitates cellular communication (25). It is a transmembrane glycoprotein in the immunoglobulin superfamily and is expressed on epithelial cells such as those found in the adenoids and respiratory system and on a variety of immune cells (26).…”

mentioning

confidence: 99%

“…LDL receptors are structurally and functionally unrelated to ICAM-1 (30) and are not known to interfere with immune responses (27,31). Previous studies examining antibody responses in naturally infected human populations (11) and T-cell immunogenic responses in murine lymphoid dendritic cells (25) demonstrate that minor-group viruses are more effective than major-group viruses in stimulating an immune response.…”

mentioning

confidence: 99%

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Human Rhinovirus Diversity and Evolution: How Strange the Change from Major to Minor

Lewis-Rogers

Seger

Adler

2017

J Virol

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Rhinoviruses are the most common causes of the common cold. Their many distinct lineages fall into "major" and "minor" groups that use different cell surface receptors to enter host cells. Minor-group rhinoviruses are more immunogenic in laboratory studies, although their patterns of transmission and their cold symptoms are broadly similar to those of the major group. Here we present evolutionary evidence that minor-group viruses are also more immunogenic in humans. A key finding is that rates of amino acid substitutions at exposed sites in the capsid proteins VP2, VP3, and VP1 tend to be elevated in minor-group relative to majorgroup viruses, while rates at buried sites show no consistent differences. A reanalysis of historical virus watch data also indicates a higher immunogenicity of minor-group viruses, consistent with our findings about evolutionary rates at amino acid positions most directly exposed to immune surveillance. The increased immunogenicity and speed of evolution in minor-group lineages may contribute to the very large numbers of rhinovirus serotypes that coexist while differing in virulence.IMPORTANCE Most colds are caused by rhinoviruses (RVs). Those caused by a subset known as the minor-group members of rhinovirus species A (RV-A) are correlated with the inception and aggravation of asthma in at-risk populations. Genetically, minor-group viruses are similar to major-group RV-A, from which they were derived, although they tend to elicit stronger immune responses. Differences in their rates and patterns of molecular evolution should be highly relevant to their epidemiology. All RV-A strains show high rates of amino acid substitutions in the capsid proteins at exposed sites not previously identified as being immunogenic, and this increase is significantly greater in minor-group viruses. These findings will inform future studies of the recently discovered RV-C, which also appears to exacerbate asthma in adults and children. In addition, these findings draw attention to the difficult problem of explaining the long-term coexistence of many serotypes of major-and minor-group RVs.KEYWORDS human rhinovirus, immunogenicity, major-group rhinoviruses, minor-group rhinoviruses, molecular evolution C old infections are caused by more than 250 virus serotypes belonging to at least five different families. The most common cold-causing viruses are rhinoviruses (RVs) (10 to 50% of all colds), coronaviruses (10 to 15% of all colds), and influenza viruses (5 to 15% of all colds) (1, 2). Globally, RVs are the primary cause of acute upper respiratory tract infections. Although most such infections are mild, RVs can also replicate in the lower respiratory tract and exacerbate the severity of conditions such as chronic respiratory disease and asthma (3-7).Rhinoviruses are nonenveloped, positive-sense, single-stranded RNA viruses belonging to the genus Enterovirus of the family Picornaviridae that infect epithelial cells that

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Section: Figmentioning

confidence: 99%

mentioning

confidence: 99%

mentioning

confidence: 99%

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Human Rhinovirus Diversity and Evolution: How Strange the Change from Major to Minor

Lewis-Rogers

Seger

Adler

2017

J Virol

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“…In contrast, the vast majority of previous functional CD45 studies in human have been carried out on PBL. Secondly, HRV binds directly to receptors present on APC [10], and this self targeting may influence the subsequent pattern of T cell activation. Thirdly, HRV infection is extremely common: it is estimated that most individuals are infected at least two or three times per year, although the majority of infections are subclinical.…”

Section: Introductionmentioning

confidence: 99%

Responses to human rhinovirus in CD45 T cell subsets isolated from tonsil

1998

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Isotypes of CD45 have been used extensively as markers of memory and naive populations of T cells in peripheral blood. In this study, T cells were isolated from human tonsil and their proliferative response against human rhinovirus was measured. Unexpectedly, equivalent responses were found among the CD4 + CD45RA + and CD4 + CD45RO + populations of T cells. This response requires MHC class II-positive antigen-presenting cells. The time course of the T cell response in vitro was that of a classical recall response, and no proliferative response to the virus could be detected in human cord blood. These results suggest that tonsils contain a significant population of CD45RA + memory cells. The presence of this population may reflect ongoing stimulation with this common infectious agent, and the anatomical location of the T cells within the major lymphoid organ draining the naso-pharyngeal epi-thelial surface.

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“…Mucosal immunity owing to nasal immunoglobulins is also well documented following HRV infection and may play an important role in protecting against pathogens transmitted across mucosal surfaces. Cell-mediated im munity to rhinovirus infections has not been studied extensively, but is likely to provide an important compo nent of protection as well [13,14], There are more than 100 HRV serotypes, which should enable vaccination possibilities even in adults who are likely to have been exposed to only a subset of serotypes.…”

Section: Chimeric Rhinoviruses As Vaccinesmentioning

confidence: 99%

Chimeric Rhinoviruses as Tools for Vaccine Development and Characterization of Protein Epitopes

Arnold

Resnick²,

Smith³

et al. 1996

Intervirology

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Chimeric human rhinoviruses (HRVs) have the potential to serve as vaccines against a wide variety of diseases. Such vaccines can be developed optimally by generating libraries of chimeric HRVs displaying immunogens from dangerous pathogens or tumor cells in many different conformations. Extremely large numbers of conformationally defined presentations of foreign epitopes can be produced efficiently by flanking transplanted epitopes with linkers, or adapters, of small segments of randomized amino acids. In addition, the individual residues of the immunogenic sequences can be encoded in proportion to their prevalence in databases, generating composite immunogens that function as mimotopes. The diversity of sequences and conformations improves the likelihood of generating immunologically valuable vaccine candidates. Chimeric viruses thus generated can be propagated and purified to select for viruses whose growth and physical stability are like those of wild-type HRV. Viruses containing a foreign epitope in antigenically relevant conformations can then be captured by immunoselection with neutralizing antibodies directed against the foreign pathogen. Using this approach, we have been able to generate HRV chimeras that present V3 loop sequences of the human immunodeficiency virus type 1 (HIV-1) in immunologically relevant conformations. Antisera directed against such chimeras can neutralize multiple strains of HIV-1 in cell culture, suggesting that the HRV14:HIV-1 chimeras may be presenting their V3 loop sequences in manners that mimic those of multiple strains of HIV. Immunologically interesting chimeras can be examined using X-ray crystallography to yield detailed information about the structures of chimeras with immunogenic epitopes. This information may lead to a greater understanding of key functional and structural elements of immunogenicity. The chimeric HRV system allows one to present virtually any protein epitope or mimitope thereof, identify viruses with immunological characteristics that mimic those of the foreign pathogen, and examine the structures of these immunogenic sequences at the atomic level.

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Antigen processing and presentation of human rhinovirus to CD4 T cells is facilitated by binding to cellular receptors for virus

Cited by 9 publications

References 21 publications

Human Rhinovirus Diversity and Evolution: How Strange the Change from Major to Minor

Human Rhinovirus Diversity and Evolution: How Strange the Change from Major to Minor

Responses to human rhinovirus in CD45 T cell subsets isolated from tonsil

Chimeric Rhinoviruses as Tools for Vaccine Development and Characterization of Protein Epitopes

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