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| [PMID]: | 27974569 |
| [Au] Autor: | Storm RJ; Persson BD; Skalman LN; Frängsmyr L; Lindström M; Rankin G; Lundmark R; Domellöf FP; Arnberg N |
| [Ad] Endereço: | Division of Virology, Department of Clinical Microbiology, Umeå University, Umeå, Sweden. |
| [Ti] Título: | Human Adenovirus Type 37 Uses α ß and α ß Integrins for Infection of Human Corneal Cells. |
| [So] Source: | J Virol;91(5), 2017 Mar 01. | | [Is] ISSN: | 1098-5514 |
| [Cp] País de publicação: | United States |
| [La] Idioma: | eng |
| [Ab] Resumo: | Epidemic keratoconjunctivitis (EKC) is a severe, contagious ocular disease that affects 20 to 40 million individuals worldwide every year. EKC is mainly caused by six types of human adenovirus (HAdV): HAdV-8, -19, -37, -53, -54, and -56. Of these, HAdV-8, -19, and -37 use sialic acid-containing glycans as cellular receptors. αVß3, αVß5, and a few additional integrins facilitate entry and endosomal release of other HAdVs. With the exception of a few biochemical analyses indicating that HAdV-37 can interact physically with αVß5, little is known about the integrins used by EKC-causing HAdVs. Here, we investigated the overall integrin expression on human corneal cells and found expression of α2, α3, α6, αV, ß1, and ß4 subunits in human corneal epithelium and/or in a human corneal epithelial (HCE) cell line but no or less accessible expression of α4, α5, ß3, or ß5. We also identified the integrins used by HAdV-37 through a series of binding and infection competition experiments and different biochemical approaches. Together, our data suggest that HAdV-37 uses αVß1 and α3ß1 integrins for infection of human corneal epithelial cells. Furthermore, to confirm the relevance of these integrins in the HAdV-37 life cycle, we developed a corneal multilayer tissue system and found that HAdV-37 infection correlated well with the patterns of αV, α3, and ß1 integrin expression. These results provide further insight into the tropism and pathogenesis of EKC-causing HAdVs and may be of importance for future development of new antiviral drugs. Keratitis is a hallmark of EKC, which is caused by six HAdV types (HAdV-8, -19, -37, -53, -54, and -56). HAdV-37 and some other HAdV types interact with integrin αVß5 in order to enter nonocular human cells. In this study, we found that αVß5 is not expressed on human corneal epithelial cells, thus proposing other host factors mediate corneal infection. Here, we first characterized integrin expression patterns on corneal tissue and corneal cells. Among the integrins identified, competition binding and infection experiments and biochemical assays pointed out αVß1 and α3ß1 to be of importance for HAdV-37 infection of corneal tissue. In the absence of a good animal model for EKC-causing HAdVs, we also developed an system with multilayer HCE cells and confirmed the relevance of the suggested integrins during HAdV-37 infection. |
| [Mh] Termos MeSH primário: |
Infecções por Adenovirus Humanos/virologia
Adenovírus Humanos/fisiologia
Integrina alfa3beta1/fisiologia
Receptores de Vitronectina/fisiologia
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| [Mh] Termos MeSH secundário: |
Células A549
Córnea/patologia
Córnea/virologia
Seres Humanos
Receptores Virais
Ligação Viral
Internalização do Vírus
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| [Pt] Tipo de publicação: | JOURNAL ARTICLE |
[Nm] Nome de substância:
| 0 (Integrin alpha3beta1); 0 (Receptors, Virus); 0 (Receptors, Vitronectin); 0 (integrin alphavbeta1) |
| [Em] Mês de entrada: | 1705 |
| [Cu] Atualização por classe: | 170529 |
[Lr] Data última revisão:
| 170529 |
| [Sb] Subgrupo de revista: | IM |
| [Da] Data de entrada para processamento: | 161216 |
| [St] Status: | MEDLINE |
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