Characterization of molecules incorporated into virions of the human immunodeficiency virus


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A Master's thesis.
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Master (thesis) (master)
Characterization of molecules incorporated into virions of the human immunodeficiency virus
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Université de Lausanne, Faculté de biologie et médecine
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In 2018, 37.9 millions of people worldwide were currently living with the human immunodeficiency virus (HIV-1) or acquired immunodeficiency syndrome (AIDS). The introduction of long-term combination antiretroviral therapy (cART) reduced HIV-1 replication below the limit of conventional methods detection. Hence it also decreased mortality, morbidity and viral transmission. However current cART is not curative as viral rebound occurs after treatment interruption. This lifelong medication is then challenging in terms of side effects, economical cost and social discrimination. The viremia rebound might be explained by two main mechanisms: the latent reservoir and the ongoing replication but the cellular origin of these rebounding virions remains an enigma.
Recently Guzzo et al. have demonstrated that HIV virions incorporate some host cell proteins, such as α4β7 integrin and HLA-DR into their envelope during budding process. Therefore a strategy to capture, detect and characterize HIV virions coming from plasma of infected individuals could be used to determine virions origin. Indeed some host cells population, such as CD4 T cells and macrophages localized in different tissue compartments could be differentiated by specific molecules expressed on their membrane.
The expression of various molecules incorporated into virions envelope, for example activation markers (PD-L1, PD-L2), chemokine receptors (CXCR5 and CXCR3) or integrin (α4β7) has been detected by mass cytometry.
In this present master thesis, we characterized host cells molecules incorporated into HIV virions envelope coming from plasma of infected individuals at different phases of infection. We confirmed that HIV virions contain molecules known to be incorporated, such as α4β7, HLA-DR and CD44. We also found a list of new identified molecules comprising CD31, CXCR3, CXCR5, CD68, Lag3, TIGIT, PD-L1 and PD-L2; however the amount of host proteins incorporation might not depend upon the clinical phase of infection, except for CD31 which might be lower in the acute stage. These results must be confirmed using distinct approaches such as flow-virometry. Anyway this work opened up perspectives for the future, hoping that one day a cure for HIV-infected patients will be available.
human immunodeficiency virus, host proteins incorporation, virions envelope characterization, mass cytometry
Create date
07/09/2020 11:53
Last modification date
05/10/2020 6:26
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