--The HIV Nef protein appears to be involved in the development of HIV-associated nephropathy (HIVAN), researchers say.
"HIV-1 infection induces the loss of podocyte differentiation markers and increases podocyte proliferation," explained Mohammad Husain and colleagues at the Mount Sinai School of Medicine in New York City and Istituto Superiore di Sanita in Rome, Italy.
These deleterious effects are almost exclusively mediated by viral Nef, Husain and coauthors found.
The researchers created a noninfectious proviral HIV construct pseudotyped with the vesicular stomatitis virus envelope. Variations of this molecular HIV clone with nonfunctional versions of key viral genes were developed, and used to isolate the proteins responsible for HIV induced podocyte dysregulation, according to the report.
Proviral constructs with nef gene deletions had no effect on cultured podocytes, study data showed. By contrast, HIV clones that lacked functional copies of the env, rev, vif, vpr, or vpu genes were able to exert their usual proliferative effects on these cells.
Stable expression of Nef protein by a non-HIV retroviral vector was sufficient to trigger heightened podocyte proliferation (HIV-1 Nef induces proliferation and anchorage-independent growth in podocytes. Journal of the American Society of Nephrology 2002 Jul;13(7):1806-15).
"These data indicate that Nef induces multiple proliferative effects in podocytes in culture," Husain and colleagues concluded, "and that nef may therefore be an important gene in the pathogenesis of HIVAN in vivo."
The corresponding author for this report is Mohammad Husain, Box 1243, Division of Nephrology, Mount Sinai School of Medicine, One Gustave L Levy Place, New York, NY 10029, USA. E-mail: firstname.lastname@example.org.
Key points reported in this study include:
- The HIV Nef protein appears to be involved in the development of HIV associated nephropathy
- HIV infection leads to pathological increases in podocyte proliferation
- In vitro experiments suggested that these effects are almost exclusively mediated by viral Nef
This article was prepared by AIDS Weekly editors from staff and other reports.