Uticaj infekcije virusom humane imunodeficijencije na genetičku varijabilnost kliničkih izolata BK i JC poliomavirusa

Abstract

Uvod Seroepidemiološke studije pokazuju da je između 27% i 80% humane populacije inficirano sa dva poliomavirusa BK virusom (BKV) i JC virusom (JCV). Posle primarne asimptomatske infekcije, koja se obično dešava u toku ranog detinjstva, oba virusa uspostavljaju latenciju u ćelijama bubrega i gornjih partija urinarnog trakta. Sporadična asimptomatska reaktivacija oba virusa se dešava kod 0.5-20% imunokompetentnih seropozitivnih osoba. Međutim, kod imunosuprimiranih osoba njihova reaktivacija može dovesti do nastanka životno ugrožavajućih oboljenja. Reaktivacija JCV, pre svega kod pacijenata sa T ćelijskom imunodeficijencijom, dovodi do litičke infekcije oligodendrocita u centralnom nervnom sistemu (CNS) i nastanka progresivne multifokalne leukoencefalopatije (PML), dok reaktivacija BKV dovodi do nastanka hemoragijskog cistitisa i poliomavirus-udružene nefropatije. Pre epidemije AIDS-a, limfoproliferativna oboljenja su bila vodeći uzrok reaktivacije JCV i BKV, dok danas HIV infekcija predstavlja najčešći uzrok reaktivacije JCV i nastanka PML. Očigledno je da imunosupresija predstavlja fundamentalni predisponirajući faktor za nastanak PML, poliomavirus-udružene nefropatije i hemoragijskog cistitisa. Ipak, ova oboljenja ne nastaju kod svih imunosuprimiranih osoba, tako da se smatra da i drugi faktori, poput genetičke varijabilnosti BK i JC virusa, mogu doprineti njihovom nastanku. Ciljevi Ciljevi ovog istraživanja bili su: da se odredi prevalenca izlučivanja BKV i JCV u urinu HIV-inficiranih pacijenata i pacijenata kontrolne grupe i ispita moguća povezanost virurije u grupi HIV-inficiranih sa demografskim, virusološkim i citološkim parametrima kao i sa stadijumima bolesti i vrstom primenjene terapije; da se utvrdi distribucija genotipova i subtipova, struktura nekodirajućeg regulatornog regiona kao i prisustvo mutacija u VP1 regionu JCV i BKV u obe grupe ispitanika...

Introduction Seroepidemiologic studies have shown that between 27% and 80% of human population is infected with two human polyomaviruses BK virus (BKV) and JC virus (JCV). After primary asymptomatic infection, which usually occurs during early childhood, both viruses establish latency in the cells of the kidney and upper parts of the urinary tract. Sporadic asymptomatic reactivations of both viruses occur in 0,5-20% of seropositive immunocompetent individuals. However, in immunosuppressed patients reactivation of the viruses can lead to the development of serious and life threatening diseases. Reactivation of JCV, primarily in patients with T cell immunodeficiency, leads to lytic infection of oligodendrocytes in the central nervous system (CNS) and the development of progressive multifocal leukoencephalopathy (PML), while reactivation of BKV is associated with hemorrhagic cystitis and polyomavirus-associated nephropathy. Before the AIDS epidemic, lymphoproliferative diseases were the leading cause for reactivation of JCV and BKV while nowdays HIV infection is the most common cause for reactivation of JCV and the development of PML. It is evident that immunosuppression is a fundamental predisposing factor for developing PML, polyomavirus-associated nephropathy and hemorrhagic cystitis. However, these diseases do not affect all immunosuppressed individuals, suggesting that other factors, such as genetic variability of BK and JC viruses, can contribute to their occurrence. Objectives The objectives of this research were to determine the prevalence of BKV and JCV viruria in HIV-infected patients and patients of the control group and critically evaluate the relationship between viruria and demographic, virological and cytological parameters as well as the stages of the disease and the applied therapy; also, to determine the distribution of genotypes and subtypes, the structure of noncoding regulatory region and the presence of mutations in the VP1 region of JCV and BKV in both groups of patients...