Báo cáo khoa học: Conserved positive selection signals in gp41 across multiple subtypes and difference in selection signals detectable in gp41 sequences sampled during acute and chronic HIV-1 subtype C infection

Tuyển tập báo cáo các nghiên cứu khoa học quốc tế ngành y học dành cho các bạn tham khảo đề tài: Conserved positive selection signals in gp41 across multiple subtypes and difference in selection signals detectable in gp41 sequences sampled during acute and chronic HIV-1 subtype C infection
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Báo cáo khoa học: "Conserved positive selection signals in gp41 across multiple subtypes and difference in selection signals detectable in gp41 sequences sampled during acute and chronic HIV-1 subtype C infection"Virology Journal BioMed Central Open AccessResearchConserved positive selection signals in gp41 across multiplesubtypes and difference in selection signals detectable in gp41sequences sampled during acute and chronic HIV-1 subtype CinfectionGama P Bandawe*1, Darren P Martin1, Florette Treurnicht1, Koleka Mlisana2,Salim S Abdool Karim2, Carolyn Williamson1 and The CAPRISA 002 AcuteInfection Study Team2Address: 1Institute of Infectious Disease and Molecular Medicine, Faculty of Health Sciences, University of Cape Town, Anzio Road, Observatory,7925, South Africa and 2Doris Duke Medical Research Institute, Nelson R Mandela School of Medicine, University of KwaZulu-Natal, Private BagX7, Congella, 4013, South AfricaEmail: Gama P Bandawe* - gama.bandawe@uct.ac.za; Darren P Martin - darrin.martin@uct.ac.za;Florette Treurnicht - florette.treurnicht@uct.ac.za; Koleka Mlisana - mlisanak@ukzn.ac.za; Salim S Abdool Karim - karims1@ukzn.ac.za;Carolyn Williamson - carolyn.williamson@uct.ac.za; The CAPRISA 002 Acute Infection Study Team - caprisa@ukzn.ac.za* Corresponding authorPublished: 24 November 2008 Received: 29 September 2008 Accepted: 24 November 2008Virology Journal 2008, 5:141 doi:10.1186/1743-422X-5-141This article is available from: http://www.virologyj.com/content/5/1/141© 2008 Bandawe et al; licensee BioMed Central Ltd.This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0),which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. Abstract Background: The high diversity of HIV variants driving the global AIDS epidemic has caused many to doubt whether an effective vaccine against the virus is possible. However, by identifying the selective forces that are driving the ongoing diversification of HIV and characterising their genetic consequences, it may be possible to design vaccines that pre-empt some of the virus more common evasion tactics. One component of such vaccines might be the envelope protein, gp41. Besides being targeted by both the humoral and cellular arms of the immune system this protein mediates fusion between viral and target cell membranes and is likely to be a primary determinant of HIV transmissibility. Results: Using recombination aware analysis tools we compared site specific signals of selection in gp41 sequences from different HIV-1 M subtypes and circulating recombinant forms and identified twelve sites evolving under positive selection across multiple major HIV-1 lineages. To identify evidence of selection operating during transmission our analysis included two matched datasets sampled from patients with acute or chronic subtype C infections. We identified six gp41 sites apparently evolving under different selection pressures during acute and chronic HIV-1 infections. These sites mostly fell within functional gp41 domains, with one site located within the epitope recognised by the broadly neutralizing antibody, 4E10. Conclusion: Whereas these six sites are potentially determinants of fitness and are therefore good candidate targets for subtype-C specific vaccines, the twelve sites evolving under diversifying selection across multiple subtypes might make good candidate targets for broadly protective vaccines. Page 1 of 16 (page number not for citation purposes)Virology Journal 2008, 5:141 http://www.virologyj.com/content/5/1/141 believed to experience extremely severe population bottle-BackgroundDetailed characterisation of the selective ...