Abstract
BackgroundThe interferon-inducible factor BST-2/tetherin blocks the release of nascent virions from the surface of infected cells for certain enveloped virus families. The primate lentiviruses have evolved several counteracting mechanisms which, in the case of HIV-2, is a function of its Env protein. We sought to further understand the features of the Env protein and tetherin that are important for this interaction, and to evaluate the selective pressure on HIV-2 to maintain such an activity.ResultsBy examining Env mutants with changes in the ectodomain of the protein (virus ROD14) or the cytoplasmic tail (substitution Y707A) that render the proteins unable to counteract tetherin, we determined that an interaction between Env and tetherin is important for this activity. Furthermore, this Env-tetherin interaction required an alanine face in the tetherin ectodomain, although insertion of this domain into an artificial tetherin-like protein was not sufficient to confer sensitivity to the HIV-2 Env. The replication of virus carrying the ROD14 substitutions was significantly slower than the matched wild-type virus, but it acquired second-site mutations during passaging in the cytoplasmic tail of Env which restored the ability of the protein to both bind to and counteract tetherin.ConclusionsThese results shed light on the interaction between HIV-2 and tetherin, suggesting a physical interaction that maps to the ectodomains of both proteins and indicating a strong selection pressure to maintain an anti-tetherin activity in the HIV-2 Env.
Highlights
The interferon-inducible factor BST-2/tetherin blocks the release of nascent virions from the surface of infected cells for certain enveloped virus families
Interaction of HIV‐2 Env and tetherin is required for tetherin antagonism Previously, it was reported that the Env protein from HIV-2 strain ROD10 can be co-immunoprecipitated with tetherin [37]
The ROD14 Env differs from ROD10 Env at 5 specific amino acids, and contains a 30 amino acid deletion in its cytoplasmic tail [40], with substitutions K422R and A598T in the ectodomain of the protein being primarily responsible for its loss of tetherin antagonism [41]
Summary
The interferon-inducible factor BST-2/tetherin blocks the release of nascent virions from the surface of infected cells for certain enveloped virus families. Tetherin/BST-2 is a multi-functional cellular protein that plays roles in cell membrane organization, as well as contributing to both the sensing and inhibition of enveloped virus replication [reviewed in 1]. In HIV-1 infected cells, tetherin retains newly assembled virions at the cell surface which both reduces the production of cell-free virus [8, 10]. The human form of tetherin, and to a lesser extent chimpanzee tetherin, can act as pattern recognition receptors, since cross-linking of the protein by tethered virions or antibodies activates the NF-κB pathway and promotes entry into an antiviral state [14, 15]
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Free) 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call
