The Role of Caveolin 1 in HIV Infection and Pathogenesis

Abstract

Caveolin 1 (Cav-1) is a major component of the caveolae structure and is expressed in a variety of cell types including macrophages, which are susceptible to human immunodeficiency virus (HIV) infection. Caveolae structures are present in abundance in mechanically stressed cells such as endothelial cells and adipocytes. HIV infection induces dysfunction of these cells and promotes pathogenesis. Cav-1 and the caveolae structure are believed to be involved in multiple cellular processes that include signal transduction, lipid regulation, endocytosis, transcytosis, and mechanoprotection. Such a broad biological role of Cav-1/caveolae is bound to have functional cross relationships with several molecular pathways including HIV replication and viral-induced pathogenesis. The current review covers the relationship of Cav-1 and HIV in respect to viral replication, persistence, and the potential role in pathogenesis.

Keywords: HIV; caveolae; caveolin 1; cholesterol; endothelial cell dysfunction; macrophages; persistent infection.

Figure 1

A model for bidirectional interplay between human immunodeficiency virus (HIV) infection and Caveolin 1 (Cav-1) in establishing persistent infection in macrophages by three mechanisms. HIV infection up-regulates the expression of Cav-1 and the enhanced level of Cav-1 subsequently represses virus replication by suppressing the activity of nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB), countering viral negative factor (Nef) and promoting apolipoprotein A-I (apoA-I) mediated cholesterol efflux, subsequently reducing available cholesterol within the cell, and blocking the fusion steps of virus infectivity. Env: envelope; Tat: transactivator.

Figure 2

HIV influence on aortic endothelial cell Cav-1 functions and potential link to pathogenesis. Viral proteins released from infected cells in combination with the induction of cellular factors such as cytokines and chemokines in the microenvironment can promote changes in Cav-1 cell distribution that impairs high-density lipoprotein (HDL) mediated cholesterol efflux and endothelial nitric oxide synthase (eNOS) regulation. There is also a reduction in eNOS, which could be related to Cav-1 redistribution. The mechanosensing function of Cav-1 may be an alternative or additional mechanism that leads to Cav-1 redistribution. These HIV induced endothelial cell dysfunctions through Cav-1 can be contributing factors to vascular diseases in HIV infected individuals.