HIV-1 and Kidney Cells: Better Understanding of Viral Interaction

Abstract

HIV-associated nephropathy (HIVAN) is the most common disease affecting untreated seropositive patients of African descent. Besides genetic (African descent) and HIV-1 infection (environmental), specific host factors such as activation of renin-angiotensin-aldosterone system (RAAS) have also been demonstrated to play a role in the manifestation of HIVAN. The recent identification of MYH9 as susceptible allele is a key step forward in our understanding for the pathogenesis of focal glomerulosclerosis in people of African-American descent. HIV-1 transgenic models have significantly advanced our knowledge base in terms of role of HIV-1 genes in general and individual gene in particular in the development of renal lesions mimicking HIVAN. These studies suggest that viral replication is not needed for the development of renal lesions. Renal biopsy data from HIVAN patients suggest that renal epithelial cells express HIV-1 genes and thus it may be sufficient to invoke HIVAN phenotype in the presence of specific host and genetic factors. On the other hand, immune response to infection may be required to induce HIV-1 associated immune complex kidney disease (HIVICK). Since renal cell lack conventional HIV-1 receptors, HIV-1 entry into renal cells has been a mystery. Recently, non-conventional pathways have been demonstrated to facilitate HIV-1 entry into renal cells in in vitro studies. These include presence of DEC-205 receptors in renal tubular cells and lipid rafts in podocytes. However, HIV-1 entry through these pathways only allows non-productive infection. It appears that the presence of specific genetic and host factors in in vivo conditions may be facilitating the development of the productive HIV-1 infection in kidney cells.

HIV-induced kidney cell injury: role of ROS-induced downregulated vitamin D receptor

“…Renal tubular cells have been demonstrated to generate ANG II production both in in vitro and in vivo studies (9,36). Renal tissue ANG II concentration has been reported to be several-fold greater than systemic ANG II concentration as a consequence of its production by kidney cells (38).…”

“…Development of HIVAN requires the presence of genetic (black ancestry in general and presence of APOL1 gene in particular), environmental (HIV infection), and specific host factors [such as activation of the renin-angiotensin system (RAS)] (35,36). On that account, blockade of angiotensin type 1 receptors or inhibition of the production of ANG II are commonly used therapeutic modalities to slow down the progression of HIVAN (1,2).…”

Pseudotype-Independent Nonspecific Uptake of Gammaretroviral and Lentiviral Particles in Human Cells

“…As we also found nonspecific internalization for MLV enveloped with measles virus H and F glycoproteins and ''bald'' lentiviral particles, nonspecific endocytosis seemed to occur independently of the particle pseudotype and capsid. Indeed, nonproductive internalization of HIV-1 carrying its natural Env was shown to occur in human renal cells (Mikulak and Singhal, 2010) and neural cells (Alvarez Losada et al, 2002) lacking the HIV-1 receptor CD4. Furthermore, nonproductive endocytosis of HIV-1 pseudotyped with natural Env seems to occur in parallel to the main route of HIV-1 infectious entry by plasma membrane fusion (Marechal et al, 1998;Schaeffer et al, 2001).…”

Renal disease in HIV-infected individuals

“…HIV mediates dysregulation of glomerular podocytes, the epithelial cells which maintain the glomerular basement membrane, and apotosis of renal tubular cells. The resulting lesion of HIVAN is a focal glomerulosclerosis (FGS) and microytic dilation of tubules [14**][15]. …”