Objetivo One of the main problems in identification of human genetic factors involved in the control of HIV-1 infection and establishing their relationships with AIDS progression is the immense natural genetic diversity of HIV-1. As various virus genetic factors alter the course of disease, identification of the role of a specific human genetic factor to control HIV-1 infection is obscured by multiple confounding effects of virus diversity. Even for the few HLA markers, which have been associated with altered disease course at the population level, there is no direct evidence that this association is indeed mediated through altered immune control of HIV-1 in individual patients, as virus diversity makes it impossible to quantify and compare CTL responses in infected patients against epitopes present in viruses of these particular patients, rather than against epitopes of reference viruses. Considering the problems caused by HIV-1 diversity in identifying human genetic markers involved in immune control of HIV-1 infection, cases of single-source infection of genetically diverse individuals by the same virus are of specific interest. However, the described cases of single-source infections have so far been limited to a few infected individuals each, thus not allowing robust studies.We identified a unique single-source outbreak of HIV-1, in which more than 1,000 individuals in Svetlogorsk were infected by an HIV-1 strain in 1996-1997. Analysis of 20 randomly selected individuals demonstrated that 75% of them are infected by viruses, which are completely identical in the genomic regions studied (env and gag). We intend to utilise this unprecedented opportunity to study the associations of specific human genetic markers with altered disease progression profiles and to assess the role of human genetic factors in defining the immune response to HIV-1 in a genetically heterogeneous human population infected by a virus from a single source, when confounding effects of genetic diversity of infecting viruses are naturally eliminated. The genome of the founder Svetlogorsk virus will be sequenced from 1996 samples and used to develop a specific peptide approach to study CTL responses against the same infecting virus in genetically different individuals (n=200) nine years after the moment of infection, in relation to individual genetic background (HLA types and HIV-1 co-receptor polymorphism), clinical (AIDS stage), virological (virus load), and immunological (CD4+ cell count) status.Attention will be given to identification of alterations of CTL epitopes of the same virus that are associated with virus escape from immune pressure, in relation to host genotype, which will be studied by sequencing late viruses in the same individuals. The epidemiological significance of these escape mutants for other HIV-1 outbreaks in Eastern Europe will be studied by using sample bank and virus genetic database, which is already in our collection and will be extended in this study. Palabras clave Epidemiology Human Genetics Immunology Programa(s) IC-INTAS - International Association for the promotion of cooperation with scientists from the independent states of the former Soviet Union (INTAS), 1993- Tema(s) Data not available Convocatoria de propuestas Data not available Régimen de financiación Data not available Coordinador UNIVERSITY OF AMSTERDAM Aportación de la UE Sin datos Dirección MEIBERGDREEF, 15 AMSTERDAM Países Bajos Ver en el mapa Coste total Sin datos Participantes (3) Ordenar alfabéticamente Ordenar por aportación de la UE Ampliar todo Contraer todo INSTITUTE OF VIROLOGY Rusia Aportación de la UE Sin datos Dirección GAMALEYA ST., 16 MOSCOW Ver en el mapa Coste total Sin datos LITHUANIAN AIDS CENTRE Lituania Aportación de la UE Sin datos Dirección NUGALETOJU STR., 14 VILNIUS Ver en el mapa Coste total Sin datos RESEARCH INSTITUTE FOR EPIDEMIOLOGY AND MICROBIOLOGY Bielorrusia Aportación de la UE Sin datos Dirección FILIMONOVA, 23 MINSK Ver en el mapa Coste total Sin datos
