Novel role of HIV-1 Nef in regulating the ubiquitination of cellular proteins.

Our recent data established that HIV-1 Nef is pivotal in determining the fate of cellular proteins by modulating ubiquitination. However, it is unknown which proteins are ubiquitinated in the presence of Nef, a question critical for understanding the proliferation/restriction strategies of HIV-1 in infected cells. To identify cellular proteins ubiquitinated by Nef, we conducted a proteomic analysis of cellular proteins in the presence and absence of Nef. Proteomic analysis in HEK293T cells indicated that 93 proteins were upregulated and 232 were downregulated in their ubiquitination status by Nef. Computational analysis classified these proteins based on molecular function, biological process, subcellular localization, and biological pathway. Of those proteins, we found a majority of molecular functions to be involved in binding and catalytic activity. With respect to biological processes, a significant portion of the proteins identified were related to cellular and metabolic processes. Subcellular localization analysis showed the bulk of proteins to be localized to the cytosol and cytosolic compartments, which is consistent with the known function and location of Nef during HIV-1 infection. As for biological pathways, the wide range of affected proteins was denoted by the multiple modes to fulfill function, as distinguished from a strictly singular means, which was not detected. Among these ubiquitinated proteins, six were found to directly interact with Nef, wherein two were upregulated and four downregulated. We also identified 14 proteins involved in protein stability through directly participating in the Ubiquitin Proteasome System (UPS)-mediated proteasomal degradation pathway. Of those proteins, we found six upregulated and eight downregulated. Taken together, these analyses indicate that HIV-1 Nef is integral to regulating the stability of various cellular proteins via modulating ubiquitination. The molecular mechanisms directing Nef-triggered regulation of cellular protein ubiquitination are currently under investigation.

An investigation of the longitudinal relationship between neighbourhood income inequality and individual self-rated health in England.

There are mixed findings on whether neighbourhood income inequality leads to better self-rated health (SRH) or not. This study considers two hypotheses: individuals living in more unequal neighbourhoods have better SRH and the level of neighbourhood income inequality and its impact on SRH is moderated by household and neighbourhood level income related variables. Data from Waves 8-10 of the UK Household Longitudinal Study for respondents living in England at wave 8 were used. Neighbourhood income inequality was measured using Gini coefficients of household income from the Pay As You Earn and benefits systems for Lower Super Output Areas. Longitudinal ordinal multilevel models predicted self-rated health in 2016-18, 2017-19 and 2019-20 by income inequality and its interaction with household income, neighbourhood median income and neighbourhood deprivation, conditional on individual educational attainment, age, sex, ethnic group, years lived in current residence, region of residence and study wave. There were 24,889 respondents analysed over three waves. SRH was worse for those living in more income equal neighbourhoods. There was no indication that neighbourhood inequality was moderated by household income, neighbourhood median income or neighbourhood deprivation. These findings are in line with the balance of existing evidence and support policy interventions that aim to create mixed communities for the purpose of improving population health.

HIV-1-Mediated Acceleration of Oncovirus-Related Non-AIDS-Defining Cancers.

With the advent of combination antiretroviral therapy (cART), overall survival has been improved, and the incidence of acquired immunodeficiency syndrome (AIDS)-defining cancers has also been remarkably reduced. However, non-AIDS-defining cancers among human immunodeficiency virus-1 (HIV-1)-associated malignancies have increased significantly so that cancer is the leading cause of death in people living with HIV in certain highly developed countries, such as France. However, it is currently unknown how HIV-1 infection raises oncogenic virus-mediated cancer risks in the HIV-1 and oncogenic virus co-infected patients, and thus elucidation of the molecular mechanisms for how HIV-1 expedites the oncogenic viruses-triggered tumorigenesis in the co-infected hosts is imperative for developing therapeutics to cure or impede the carcinogenesis. Hence, this review is focused on HIV-1 and oncogenic virus co-infection-mediated molecular processes in the acceleration of non-AIDS-defining cancers.