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Human Adenovirus Type 26 Infection Mediated by αvß3 Integrin Is Caveolin-1-Dependent.
Nestic, Davor; Custers, Jerome; Svec, Danijel; Majhen, Dragomira.
  • Nestic D; Division of Molecular Biology, Ruder Boskovic Institute, Zagreb, Croatia.
  • Custers J; Viral Vaccine Discovery and Early Development, Janssen Vaccines and Prevention BV, Leiden, The Netherlands.
  • Svec D; Division of Molecular Biology, Ruder Boskovic Institute, Zagreb, Croatia.
  • Majhen D; Division of Molecular Biology, Ruder Boskovic Institute, Zagreb, Croatia.
Microbiol Spectr ; 10(4): e0109722, 2022 08 31.
Article in English | MEDLINE | ID: covidwho-2325199
ABSTRACT
Human adenovirus type 26 (HAdV26) has been recognized as a promising platform for vaccine vector development, and very recently vaccine against COVID-19 based on HAdV26 was authorized for emergency use. Nevertheless, basic biology of this virus, namely, pathway which HAdV26 uses to enter the cell, is still insufficiently known. We have shown here that HAdV26 infection of human epithelial cells expressing low amount of αvß3 integrin involves clathrin and is caveolin-1-independent, while HAdV26 infection of cells with high amount of αvß3 integrin does not involve clathrin but is caveolin-1-dependent. Thus, this study demonstrates that caveolin-1 is limiting factor in αvß3 integrin-mediated HAdV26 infection. Regardless of αvß3 integrin expression, HAdV26 infection involves dynamin-2. Our data provide for the first-time description of HAdV26 cell entry pathway, hence increase our knowledge of HAdV26 infection. Knowing that functionality of adenovirus vector is influenced by its cell entry pathway and intracellular trafficking, our results will contribute to better understanding of HAdV26 immunogenicity and antigen presentation when used as vaccine vector. IMPORTANCE In order to fulfill its role as a vector, adenovirus needs to successfully deliver its DNA genome to the host nucleus, a process highly influenced by adenovirus intracellular translocation. Thus, cell entry pathway and intracellular trafficking determine functionality of human adenovirus-based vectors. Endocytosis of HAdV26, currently extensively studied as a vaccine vector, has not been described so far. We present here that HAdV26 infection of human epithelial cells with high expression of αvß3 integrin, one of the putative HAdV26 receptors, is caveolin-1- and partially dynamin-2-dependent. Since caveolin containing domains provide a unique environment for specific signaling events and participate in inflammatory signaling one can imagine that directing HAdV26 cell entry toward caveolin-1-mediate pathway might play role in immunogenicity of this virus. Therefore, our results contribute to better understanding of HAdV26 infection pathway, hence, can be helpful in explaining induction of immune response and antigen presentation by HAdV26-based vaccine vector.
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Full text: Available Collection: International databases Database: MEDLINE Main subject: Adenoviruses, Human / COVID-19 Topics: Vaccines Limits: Humans Language: English Journal: Microbiol Spectr Year: 2022 Document Type: Article Affiliation country: Spectrum.01097-22

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Full text: Available Collection: International databases Database: MEDLINE Main subject: Adenoviruses, Human / COVID-19 Topics: Vaccines Limits: Humans Language: English Journal: Microbiol Spectr Year: 2022 Document Type: Article Affiliation country: Spectrum.01097-22