Modulation of the NF-κB signaling pathway by the HIV-2 envelope glycoprotein and its incomplete BST-2 antagonism

Abstract

The HIVs have evolved by selecting means to hijack numerous host cellular factors. HIVs exploit the transcription factor NF-κB to ensure efficient LTR-driven gene transcription. However, NF-κB is primarily known to act as a key regulator of the proinflammatory and antiviral responses. Interestingly, retroviruses activate NF-κB during early stages of infection to initiate proviral genome expression while suppressing it at later stages to restrain expression of antiviral genes. During HIV-1 infection, diverse viral proteins such as Env, Nef and Vpr have been proposed to activate NF-κB activity, whereas Vpu has been shown to inhibit NF-κB activation. It is still unclear how HIV-2 regulates NF-κB signaling pathway during its replication cycle. Here we confirm that human BST-2 and HIV-1 Env proteins can trigger potent activation of NF-κB. Importantly, we demonstrate for the first time that the HIV-2 Env induces NF-κB activation in HEΚ293T cells. Furthermore, the anti-BST-2 activity of the HIV-2 Env is not sufficient to completely inhibit NF-κB activity.

Sendai Virus, a Strong Inducer of Anti-Lentiviral State in Ovine Cells

“…The different antiviral programming that SeV-GFP induced in OSF is characterized by faint inductions of RIG-I and BST2 and not the expression of A3Z1, and may account for this restriction pattern ( Figure 5 ). While RIG-I is a typical ISG involved in viral dsRNA recognition and the induction of IFN, and antiviral responses, BST-2, as a transmembrane protein, is able to block the budding of emerging virus particles from the plasma membrane, thereby reducing cell-to-cell transmission without affecting other restriction sites or signaling events [ 48 ]. Despite differences at the DNA and virus production levels, SRLV mRNA levels were not affected by SeV infection.…”

Limiting Respiratory Viral Infection by Targeting Antiviral and Immunological Functions of BST‐2/Tetherin: Knowledge and Gaps

“…HIV‐1 Vpu, which targets BST‐2 for surface removal and destruction, also prevents BST‐2‐mediated activation of NF‐κB . However, Ebola GP and HIV2 Env, which engage BST‐2 to inhibit its viral tethering ability but do not direct its degradation, do not inhibit this signaling ability of BST‐2 . The impact of antagonists encoded by respiratory viruses on BST‐2‐mediated NF‐κB activation has not been investigated.…”

Different Subtypes of Influenza Viruses Target Different Human Proteins and Pathways Leading to Different Pathogenic Phenotypes

“…Some pathogenic microorganisms activate NF- κ B for viral gene expression, replication and spread. For example, the K15 protein of KSHV and the early protein Nef of most primate lentiviruses enhances NF- κ B activation to initiate proviral transcription [17, 18]. IAVs can also interfere with antiviral responses by regulating the NF- κ B signaling pathway.…”