Genetic variations in the host dependency factors ALCAM and TPST2 impact HIV-1 disease progression
| Autor: | Irma Maurer, Zita Kruize, Thijs Booiman, Brigitte Boeser-Nunnink, Neeltje A. Kootstra |
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| Přispěvatelé: | Internal medicine, Graduate School, AII - Infectious diseases, APH - Aging & Later Life, Experimental Immunology |
| Jazyk: | angličtina |
| Rok vydání: | 2020 |
| Předmět: |
Adult
Fetal Proteins Male 0301 basic medicine Cell Adhesion Molecules Neuronal Immunology HIV Infections Single-nucleotide polymorphism Biology Polymorphism Single Nucleotide Men who have sex with men Pathogenesis 03 medical and health sciences 0302 clinical medicine Antigens CD Activated-Leukocyte Cell Adhesion Molecule Genetic variation Humans Immunology and Allergy 030212 general & internal medicine Homosexuality Male Gene ALCAM Survival analysis Netherlands Membrane Proteins Middle Aged Survival Analysis Minor allele frequency 030104 developmental biology Infectious Diseases Disease Progression HIV-1 Sulfotransferases |
| Zdroj: | Kruize, Z, Maurer, I, Boeser-Nunnink, B D M, Booiman, T & Kootstra, N A 2020, ' Genetic variations in the host dependency factors ALCAM and TPST2 impact HIV-1 disease progression ', AIDS (London, England), vol. 34, no. 9, pp. 1303-1312 . https://doi.org/10.1097/QAD.0000000000002540 AIDS (London, England), 34(9), 1303-1312 AIDS (London, England), 34(9), 1303-1312. Lippincott Williams and Wilkins |
| ISSN: | 0269-9370 1473-5571 |
| Popis: | OBJECTIVES: Recently, the activated leukocyte cell adhesion molecule (ALCAM) and tyrosylprotein sulfotransferase 2 (TPST2) have been identified as important host dependency factors (HDFs) for in-vitro HIV-1 replication. To determine whether these genes play a role in HIV-1 pathogenesis, we analysed whether naturally occurring genetic variations were associated with the clinical course of infection. DESIGN/METHODS: Single nucleotide polymorphisms (SNPs) in ALCAM and TPST2 were analysed in a cohort of 304 HIV-1-infected men who have sex with men and survival analysis was used to determine their effect on the outcome of untreated HIV-1 infection. Flowcytometry was used to determine the effect of SNPs on CD4 T-cell activation prior to HIV-1 infection and 1 and 5 years after infection. In-vitro HIV-1 infections were performed to analyse the effect of the SNPs on HIV-1 replication. RESULTS: We observed that the minor allele of rs1344861 in ALCAM was associated with accelerated disease progression, whereas the minor allele of rs9613199 in TPST2 was associated with delayed disease progression. In-vitro infection assays did not demonstrate any differences in HIV-1 replication associated with rs9613199. However, the increase in CD4 T-cell immune activation levels during HIV-1 infection was less pronounced in infected individuals homozygous for rs9613199, which is in agreement with delayed disease progression. CONCLUSION: Our data demonstrate that ALCAM and TPST2 play a role in HIV-1 pathogenesis. SNPs in these genes, without known functional implications, had a major effect on disease progression, and therefore, these HDFs may be attractive and effective targets for new treatment strategies. |
| Databáze: | OpenAIRE |
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