Host and Viral Factors in HIV-Mediated Bystander Apoptosis

Abstract

Human immunodeficiency virus (HIV) infections lead to a progressive loss of CD4 T cells primarily via the process of apoptosis. With a limited number of infected cells and vastly disproportionate apoptosis in HIV infected patients, it is believed that apoptosis of uninfected bystander cells plays a significant role in this process. Disease progression in HIV infected individuals is highly variable suggesting that both host and viral factors may influence HIV mediated apoptosis. Amongst the viral factors, the role of Envelope (Env) glycoprotein in bystander apoptosis is well documented. Recent evidence on the variability in apoptosis induction by primary patient derived Envs underscores the role of Env glycoprotein in HIV disease. Amongst the host factors, the role of C-C Chemokine Receptor type 5 (CCR5), a coreceptor for HIV Env, is also becoming increasingly evident. Polymorphisms in the CCR5 gene and promoter affect CCR5 cell surface expression and correlate with both apoptosis and CD4 loss. Finally, chronic immune activation in HIV infections induces multiple defects in the immune system and has recently been shown to accelerate HIV Env mediated CD4 apoptosis. Consequently, those factors that affect CCR5 expression and/or immune activation in turn indirectly regulate HIV mediated apoptosis making this phenomenon both complex and multifactorial. This review explores the complex role of various host and viral factors in determining HIV mediated bystander apoptosis.

HIV-1 subtype CRF01_AE and B differ in utilization of low levels of CCR5, Maraviroc susceptibility and potential N-glycosylation sites

“…The marked variability in the course and manifestation of HIV disease can be attributed to several host factors as well as viral determinants (Garg and Joshi, 2017). One of the key factors contributing to this variability is the remarkable genetic heterogeneity of HIV-1 (Tebit et al, 2007) which has led to the evolution of several subtypes and CRFs since its introduction into the human population.…”

Provision of combined antiretroviral therapy in HIV-positive pregnant women and the increased risk of apoptosis-related intra-uterine growth restriction

“…Excessive ROS production causes oxidative stress, which is commonly found during infectious inflammation. Oxidative stress damages cellular structures, including lipids, proteins and DNA [30][31][32]. Mitochondria are the major source of ROS during oxidative phosphorylation.…”

Characteristics of Levels of Serum Markers of Apoptosis Fas-Systems in Hiv-Mono-Infected Persons, Patients With Hiv/HCV-Co-Infection and Chronic Viral Hepatitis C

“…Более того, существуют данные о том, что gp 41 облегчает гемифузию мембран близлежащих клеток, тем самым увеличивая количество лимфоцитов, подвергшихся апоптозу. Белок Nef усиливает экспрессию FasL (CD95L) на мембранах инфицированных клеток, что при взаимодействии инфицированных и неинфицированных лимфоцитов провоцирует апоптоз последних, на поверхности которых расположен CD95 (Fas) [3][4][5]. После развития СПИДа происходит снижение концентрации sFasL в крови, что наиболее вероятно связано со значительным истощением пула CD4+-лимфоцитов [4][5][6].…”

“…Белок Nef усиливает экспрессию FasL (CD95L) на мембранах инфицированных клеток, что при взаимодействии инфицированных и неинфицированных лимфоцитов провоцирует апоптоз последних, на поверхности которых расположен CD95 (Fas) [3][4][5]. После развития СПИДа происходит снижение концентрации sFasL в крови, что наиболее вероятно связано со значительным истощением пула CD4+-лимфоцитов [4][5][6]. При этом исследования белорусских коллег показали, что концентрация растворимой формы рецептора Fas (sFas/APO-1/CD95) увеличивается соответственно стадии ВИЧ-инфекции [7,8].…”