Prevalence a role CCR5Δ32 v progresi onemocnění u HIV pozitivních pacientů v České republice

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Autoři: L. Sácká ¹; J. Hodek ¹; L. Machala ²; M. Malý ³; J. Weber ¹
Působiště autorů: Institute of Organic Chemistry and Biochemistry, Czech Academy of Sciences, Prague, Czech Republic ¹; Department of Infectious Diseases, Third Faculty of Medicine, Charles University and Hospital Na Bulovce, Prague, Czech Republic ²; National Institute of Public Health, Prague, Czech Republic ³
Vyšlo v časopise: Epidemiol. Mikrobiol. Imunol. 68, 2019, č. 3, s. 138-143
Kategorie: Původní práce

Souhrn

Úvod: Vstup viru lidské imunitní nedostatečnosti typu 1 (HIV-1) do cílových buněk je umožněn CD4 receptorem a jedním ze dvou koreceptorů CXCR4 nebo CCR5. Delece úseku 32 nukleotidů v genu pro CCR5 (CCR5Δ32) v obou alelách poskytuje silnou, avšak ne absolutní odolnost proti infekci HIV-1 a delece v jedné alele zpomaluje postup nemoci směřující k rozvinutí AIDS. Zde jsme analyzovali prevalenci a roli heterozygotního výskytu CCR5Δ32 na postup onemocnění u HIV pozitivních jedinců v České republice.

Metody: Celkem 92 HIV-1 séropozitivních osob včetně 80 Čechů z AIDS centra v Nemocnici Na Bulovce v Praze bylo zařazeno do genotypizace CCR5, která byla součástí studie role HIV fitness na průběh onemocnění. Z periferních mononukleárních buněk pacienta byla získána DNA, která byla použita k amplifikaci pomocí PCR v reálném čase použitím specifických sond, které detekovaly divokou variantu CCR5 a variantu s 32 nt delecí. Podmnožina 74 pacientů bez antiretrovirové léčby, kteří byli sledováni déle než jeden rok, byla použita k určení role heterozygotního fenotypu CCR5 na průběh nemoci.

Výsledky: Heterozygotní CCR5Δ32 varianta byla nalezena u 23,8 % z 80 českých HIV-1 séropozitivních osob, což je velmi podobné jako publikovaná 21 % a 24 % prevalence u HIV negativní české populace. Homozygotní mutovaná varianta nebyla nalezena. U skupiny osob s heterozygotním CCR5 fenotypem jsme pozorovali slabě zvýšený průměrný počet CD4-pozitivních T-lymfocytů a nižší průměrné hodnoty virémie v plazmě.

Závěr: Celkově, naše studie neukázala žádný zřejmý užitek přítomnosti heterozygotní CCR5Δ32 varianty na přenos HIV a pouze malý užitek na průběh nemoci u české HIV-1 pozitivní kohorty.

Klíčová slova:

HIV-1 – koreceptor CCR5 – CCR5Δ32 – heterozygotní polymorfismus – progrese nemoci

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