HIV Infected Cells May Wreak Wide Spread Distruction On Body

HIV infection has a profinding effect on bystander cells causing metabolic co-morbidities. A single viral factor released from HIV infected cells may wreak widespread distruction on the body and lead to the development of chronic and potentially deadly diseases like heart disease, diabetes and dementia. The treatment of HIV/AIDS is so advanced that today life expectancy of people living with HIV is very similar to that of uninfected persons.

However, people with HIV may experience co-morbidities like heart disease, diabetes, dementia or related complications. Studies show that not only are people living with HIV at increased risk of these chronic diseases, they are occurring at an earlier age and progress faster. These co-morbidities persist even after successful application of antiretroviral therapy, when no virus is found in the blood. As the HIV at increased risk of these chronic diseases, they are occurring at an earlier age and progress faster.

Widespread distruction of HIV

Scientists have been intrigued as to what is going on in the small number of infected cells; believing that HIV-infected cells instead of the virus release a toxic substance that kills cells around them. Most co-morbidities of HIV infection share a common element in their pathogenesis, impairment of cholesterol metabolism but exactly how and what was happening remained a mystery. These co-morbidities persist even after successful application of antiretroviral therapy, when no virus is finding in the blood.

This impairment triggers inflammation, contributing to the development of diseases including dementia, heart disease and diabetes. The study showing that the HIV protein, Nef, releasing from infecting cells in specialised vesicles; is taking up by uninfecting ‘bystander’ cells; impairing cholesterol metabolism in these cells. Changes in rafts led to re-localization of TLR4 and TREM-1 to rafts; phosphorylation of ERK1/2, activation of NLRP3 inflammasome; and increasing secretion of pro-inflammatory cytokines.

ABCA1 in macrophages

Mice injected with exNef exhibited monocytosis, reduced ABCA1 in macrophages, increased raft abundance in monocytes and augmented inflammation. Thus, Nef-containing exosomes potentiating pro-inflammatory response by inducing changes in cholesterol metabolism and reorganizing lipid rafts. These mechanisms may contribute to HIV-associated metabolic co-morbidities.

The effects of exNef on lipid rafts and on inflammation were reversing by overexpression of a constitutively active mutant of Cdc42. This impairment triggers inflammation, contributing to the development of diseases including dementia, heart disease and diabetes. These mechanisms may contribute to HIV-associated metabolic co-morbidities. Our work demonstrates how a single viral factor released from infected cells into circulation; may cause a pleiotropy of pathogenic responses.