Cabecera 2019 CBMSO CSIC UAM

Sunday, 25th August 2019

Viral modulation of the immune response

 

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Antonio Alcamí

BSciStaff

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Research summary:

We are investigating immune evasion mechanisms employed by large DNA viruses, poxviruses and herpesviruses. Specifically, we are characterizing viral proteins that are secreted from infected cells, interact with cytokines and chemokines, and control their immunomodulatory activity. We work on two virus systems: (1) Herpesviruses like herpes simplex virus, a human pathogen of clinical relevance; and (2) Poxviruses such as vaccinia virus, the smallpox vaccine. These viral cytokine receptors have unexpected properties, enhancing the activity of chemokines or binding to the cell surface to be retained in the vicinity of infected tissues, and provide insights into the function of cytokines. The contribution of viral cytokine receptors to pathogenesis and immune modulation is being addressed in mice infected with ectromelia virus, a natural mouse pathogen that causes a smallpox-like disease known as mousepox.

fig01-300  
Virus-encoded chemokine binding proteins.  


Viruses offer a unique opportunity to develop their immune evasion strategies, optimized for millions of years of evolution, as novel therapeutic approaches. In collaboration with Biotech Companies, we are developing viral immunomodulatory proteins as potential medicaments to treat human allergic and autoimmune diseases.
We are sequencing the complete genome of large DNA viruses in order to identify new viral genes involved in pathogenesis and immune modulation, including natural isolates of ectromelia virus and new iridoviruses infecting fish and amphibian. Viruses are the most abundant and diverse biological entities on Earth. Following metagenomic approaches, we are characterizing complex viral communities using next generation sequencing methodologies (454-Roche, Illumina). We described for the first time the viral community in an Antarctic lake and are expanding these studies to other lakes along the Antarctic Peninsula and in the Arctic. Viral metagenomics is being used to identify viruses associated with human pathologies, such as multiple sclerosis.

 

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Electron micrograph of an ectromelia virus-infected cell showing inclusion body with mature virus particles.

 

 

 

 

 


 Selected Publications:

  • Alcami, A. and Moss, B. (2011) Smallpox Vaccines. In: Khan, A. S. and Smith, G. L. (eds) Scientific Review of Variola Virus Research 1999-2010. World Health Organization, Geneva, Switzerland, pp. 1-15.
  • Alejo, A., Pontejo, S. M., and Alcami, A. (2011) Poxviral TNFRs: properties and role in viral pathogenesis. Adv. Exp. Med. Biol.691, 203-210.
  • Montanuy, I., Alejo, A., and Alcami, A. (2011) Glycosaminoglycans mediate retention of the poxvirus type I interferon binding protein at the cell surface to locally block interferon antiviral responses. FASEB J. 25, 1960-1971.
  • Xu, R., Rubio, D., Roscoe, F., Krouse, T. E., Truckenmiller, M. E., Norbury, C. C., Hudson, P. N., Damon, I. K., Alcami A., and Sigal, L. J. (2012) Antibody inhibition of a viral type I interferon decoy receptor cures a viral disease by restoring interferon signaling in the liver. PLoS Pathogens 8(1):e1002475.
  • Viejo-Borbolla, A., Martinez-Martín, N., Nel, H. J., Rueda, P., Martín, R., Blanco, S., Arenzana-Seisdedos, F., Thelen, M., Fallon, P. G., and Alcami, A. (2012) Enhancement of chemokine function as an immunomodulatory strategy employed by human herpesviruses. PLoS Pathogens 8(2): e1002497.

 


 

Patents:

- Martín-Pontejo, S. y Alcami, A. Unión a glicosaminoglicanos de proteínas con dominio SECRET codificadas por poxvirus. Número de prioridad: P201230540. País: España. Fechas de prioridad: 11 abril 2012. Propietario: CSIC.
- Cabrera, J. R., Viejo-Borbolla, A., Martínez-Martín, N., Wandosell, F. y Alcami, A.. 'Proteína viral recombinante SgG2 y/o complejos binarios SgG2-FNs para su uso en crecimiento y/o regeneración axonal'. Número de p rioridad: P201231654. País: España. Fecha de prioridad: 26 octubre 2012. Propietario: CSIC.


 

Doctoral Theses:

Sergio Martín Pontejo (2012). Características moleculares y funcionales de los receptores solubles del TNF con capacidad anti-quimioquinas de poxvirus. Universidad Autónoma de Madrid. Directores: Begoña Ruiz Argüello y Antonio Alcamí.

Marcos Palomo (2012). Caracterización de inhibidores solubles de interferón codificados por poxvirus. Universidad Autónoma de Madrid. Director: Antonio Alcamí.

Nadia Martínez Martín (2012). Herpes simples virus glycoprotein G enhances chemotaxis and axonal growth through modification of plasma membrane microdomains and receptor trafficking. Universidad Autónoma de Madrid. Directores: Abel Viejo Borbolla y Antonio Alcamí.


 

Other activities:

- Member of the Editorial Board of Virology
- Member of the Editorial Board of Journal of Virology
- Advisor to the World Health Organization Advisory Committee on Variola Virus Research
- Organizer, together with R. Blasco and E. Villar, of the XIX International Poxvirus, Asfarvirus and Iridovirus Conference. Salamanca, June 2012.
- The Group participates in the Spanish Network of Multiple Sclerosis (www.reem.es)

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