The field of host-retrovirus interactions is complex and wide since multiple cellular proteins can act as positive or negative factors for viral infections or pathogenesis. In this work, we investigated the role of some cellular proteins on HIV-1 infectivity. The first examined factor is HLA-C and its potential role in AIDS progression. The analysis of the HLA-C genotype of 96 HIV-1 positive patients unveils the statistically significant association between some HLA-C variants, less stably bound to β2microglobulin/peptide complex, and a more rapid AIDS progression (p-value = 0.0143). The second considered aspect is the role of cellular proteins on HIV-associated neurocognitive disorders development (HAND). Finding new biomarkers and genetic factors linked to HIV associated neurocognitive disorders was the aim of this second study. The analyzed factors include HLA-C, Apolipoprotein E, β2microglobulin, and Neurofilament Light Chain (NFL). A cohort of 32 patients was selected for this study and the subjects were classified according to their neurocognitive status. HLA-C and Apolipoprotein E genotypes were determined through an Allele Specific PCR approach, while β2microglobulin and Neurofilament Light Chain plasma levels were quantified. Unfortunately, an association between the analyzed genetic factors/biomarkers and HAND development could not be determined due to the poor patient’s recruitment caused by the COVID-19 pandemic. The third analyzed factor is ACOT8, a thioesterase discovered as an HIV-1 Nef protein-interacting partner. To unravel ACOT8 involvement in HIV-1 infectivity pseudotyped viruses were produced using Hek293T wild type or ACOT8 knock-out cell lines. The infection step was performed using TZM-bl wild type or TZM-bl ACOT8 knock-out cell lines. This approach revealed a probable ACOT8 role on virus production and infection that will be further analyzed.

Host factors restricting HIV-1 infectivity

Chiara Stefani
2022

Abstract

The field of host-retrovirus interactions is complex and wide since multiple cellular proteins can act as positive or negative factors for viral infections or pathogenesis. In this work, we investigated the role of some cellular proteins on HIV-1 infectivity. The first examined factor is HLA-C and its potential role in AIDS progression. The analysis of the HLA-C genotype of 96 HIV-1 positive patients unveils the statistically significant association between some HLA-C variants, less stably bound to β2microglobulin/peptide complex, and a more rapid AIDS progression (p-value = 0.0143). The second considered aspect is the role of cellular proteins on HIV-associated neurocognitive disorders development (HAND). Finding new biomarkers and genetic factors linked to HIV associated neurocognitive disorders was the aim of this second study. The analyzed factors include HLA-C, Apolipoprotein E, β2microglobulin, and Neurofilament Light Chain (NFL). A cohort of 32 patients was selected for this study and the subjects were classified according to their neurocognitive status. HLA-C and Apolipoprotein E genotypes were determined through an Allele Specific PCR approach, while β2microglobulin and Neurofilament Light Chain plasma levels were quantified. Unfortunately, an association between the analyzed genetic factors/biomarkers and HAND development could not be determined due to the poor patient’s recruitment caused by the COVID-19 pandemic. The third analyzed factor is ACOT8, a thioesterase discovered as an HIV-1 Nef protein-interacting partner. To unravel ACOT8 involvement in HIV-1 infectivity pseudotyped viruses were produced using Hek293T wild type or ACOT8 knock-out cell lines. The infection step was performed using TZM-bl wild type or TZM-bl ACOT8 knock-out cell lines. This approach revealed a probable ACOT8 role on virus production and infection that will be further analyzed.
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Utilizza questo identificativo per citare o creare un link a questo documento: http://hdl.handle.net/11562/1073347
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