Entry of HIV-1 into target cells requires the sequential interaction of the viral envelope glycoprotein gp120 with the CD4 receptor and either CCR5 or CXCR4 acting as co-receptors. The viral envelope is under strong evolutionary pressure along HIV-1 infection due to both innate and adaptive immune responses: chemokines binding HIV-1 co-receptors, neutralizing antibodies and probably class I Interferon, are mechanisms driving important changes in the structure of the HIV-1 envelope in a particular HIV-1 infected patient. In support of this hypothesis it is well known that viral strains binding CCR5 (R5-tropic) and with a resistance to Interferon are preferentially transmitted, and R5-tropic viruses predominate in the early phases of infection. In contrast, those strains that use CXCR4 for entry emerge after years of infection, and this emergence correlates with a poor clinical outcome and development of AIDS. However, up to 50% of the infected individuals progress to AIDS in the presence of only R5 viruses and the mechanisms driving this selection are not fully understood so far.
In the lab we have addressed the study of the HIV-1 envelope from different perspectives and we consider the viral envelope as both a major determinant of HIV pathogenesis and a mirror of the innate and adaptive immune response elicited against HIV.
Different projects and approaches to get a better insight on the characteristics of the HIV-1 envelope are developed by Mayte Pérez-Olmeda (Senior researcher), Javier García-Pérez (Tenure Post-doc) and Nuria González (Tenure Post-doc) with the support of the technicians Almudena Cascajero, Amparo Álvarez and Laura Jiménez.
Our main contributions to this field have been:
Finally, we have written different reviews on this issue and participated in clinical guidelines:
Spanish Ministry of Health. Instituto de Salud Carlos III:
Foundation for Research and Prevention of AIDS in Spain (FIPSE):
French Agence Nationale de Recherche sur le SIDA et les Hépatites Virales (ANRS):
Thanks to the development of a new recombinant virus system carrying specific genetic sequences from patients, we had the opportunity of participating in the NEUTNET and EUROPRISE Networks supported by the European Commission. In this initiative we validated our model with gold standards in the field and collaborated closely with Gabriella Scarlatti from Università Vita-Salute San Raffaele, Milan, and Leo Heyndrick from the Instituut voor Tropische Geneeskunde, Antwerp (Fenyö EM, et al. PLoS One. 2009;4(2):e4505. and Heyndrickx L, et al. PLoS One. 2012;7(5):e36438.).
In the vaccine field, our group is the reference laboratory in the Spanish AIDS Research Network (RIS) for titration and characterization of neutralizing antibodies. We have participated in vaccine clinical trials and develop very close collaborations with teams from Hospital Clínic of Barcelona, José María Gatell, Eloisa Yuste and Sonsoles Sánchez-Palomino (Medina-Ramírez M, et al. J Virol. 2011 Jun;85(12):5804-13. and Álvarez-Fernández C, et al. PLoS One. 2012;7(11):e48848.).
We collaborate with Bernard Lagane and Fernando Arenzana-Seisdedos from Unité de Patologie Virale Molléculaire at Pasteur Institute in the study of the mechanisms driving HIV-1 evolution in vivo, and in particular, the role of chemokines in this process. These projects are funded by the French Agency on AIDS Research, ANRS, (Colin P, et al. Proc Natl Acad Sci U S A. 2013 Jun 4;110(23):9475-80.).
Finally, we have set up a tropism assay that has been validated with other tests in the field and gave us the opportunity to collaborate with the company Pfizer in the study of tropism in clinical samples and the mechanisms of resistance to Maraviroc (González N, et al. J Antimicrob Chemother. 2010 Dec;65(12):2493-501., (García-Pérez J, et al. J Biol Chem. 2011 Sep 23;286(38):33409-21. and García-Pérez J, et al. J Biol Chem. 2011 Feb 18;286(7):4978-90.).