Current HIV Research - Volume 9, Issue 7, 2011

Ever since the protein received its inappropriate acronym “negative facor”, the primate lentiviral Nef protein has opened a field of research marked by controversy. Two decades after the discovery of its importance for pathogenic infection of rhesus macaques followed by similar observations in HIV infected humans, the mechanism of action of this protein remains notoriously enigmatic, a puzzle that is solved only Read More

The Nef protein is an essential factor for lentiviral pathogenesis in humans and other simians. Despite a multitude of functions attributed to this protein, the exact role of Nef in disease progression remains unclear. One of its most intriguing functions is the ability of Nef to enhance the infectivity of viral particles. In this review we will discuss current insights in the mechanism of this well-known, yet poorly understood Nef Read More

The regulatory Nef protein of HIV-1/2 and SIV is required for high viral replication and disease progression, thus represents a very attractive therapeutic target. Because of the multi-functional nature of the Nef protein, it is unclear which of the several Nef activities are most crucial in vivo for the outcome of viral infection. Some findings indicate that the CD4 down-regulation activity of Nef is critical for viral infectivity as wel Read More

The HIV-1, HIV-2 and SIV Nef protein are known to modulate the expression of several cell surface receptors and molecules to escape the immune system, to alter T cell activation, to enhance viral replication, infectivity and transmission and overall to ensure the optimal environment for infection outcome. Consistent and continuous efforts have been made over the years to characterize the modulation of expression of ea Read More

Following transmission of human immunodeficiency virus (HIV) into a new host, cells of the monocyte/macrophage lineage play a central role in host invasion and viral replication. In particular, macrophages survive infection and support long-standing viral replication, contributing to viral persistence within the host and representing a viral reservoir in vivo. On the other hand, HIV Nef protein is a small though versatile mole Read More

The multifunctional Nef protein of primate lentiviruses is commonly considered an early viral factor that downmodulates various receptors from the cell surface and modulates several signaling pathways to facilitate viral immune evasion and to render the cell conducive for viral replication. However, Nef also acts during the late stages of infection, e.g. by increasing the infectivity of progeny virions. Just recently, it has becom Read More

CD4C/HIVNef Tg mice express HIV-1 Nef in relevant target cells through the regulatory sequences of the human CD4 gene. These mice develop a severe disease showing many characteristics of human AIDS. A summary of the results obtained with these Tg mice is presented.

A bewildering number of host cell proteins associated with Nef can be found in the literature and in the public protein interaction databases. However, only in a few of these cases, including binding of Nef to certain Src homology-3 (SH3) domain proteins, is the interaction understood in any molecular detail or even known to be direct. Indeed, SH3 binding capacity by Nef is required for many of the other protein interactio Read More

The HIV-1 Nef protein is an accessory protein of 24-27 kDa mass that mediates a multitude of effector functions in infected cells. Although not essentially required for viral replication, HIV-1 Nef exhibits stimulating potential towards disease progression to AIDS and is therefore considered a pathogenic factor in retroviridae. Here we correlate sequence conservation in HIV-1 Nef with surface hydrophobicity and functionality in Read More