Browse by author
Lookup NU author(s): Dr Christopher DuncanORCiD
Full text for this publication is not currently held within this repository. Alternative links are provided below where available.
Macrophage infection is considered to play an important role in HIV-1 pathogenesis and persistence. Using a primary cell-based coculture model, we show that monocyte-derived macrophages (MDM) efficiently transmit a high-multiplicity HIV-1 infection to autologous CD4+ T cells through a viral envelope glycoprotein (Env) receptor- and actin-dependent virological synapse (VS), facilitated by interactions between ICAM-1 and LFA-1. Virological synapse (VS)-mediated transmission by MDM results in high levels of T cell HIV-1 integration and is 1 to 2 orders of magnitude more efficient than cell-free infection. This mode of cell-to-cell transmission is broadly susceptible to the activity of CD4 binding site (CD4bs) and glycan or glycopeptide epitope-specific broadly neutralizing monoclonal antibodies (bNMAbs) but shows resistance to bNMAbs targeting the Env gp41 subunit membrane-proximal external region (MPER). These data define for the first time the structure and function of the macrophage-to-T cell VS and have important implications for bNMAb activity in HIV-1 prophylaxis and therapy.IMPORTANCE The ability of HIV-1 to move directly between contacting immune cells allows efficient viral dissemination with the potential to evade antibody attack. Here, we show that HIV-1 spreads from infected macrophages to T cells via a structure called a virological synapse that maintains extended contact between the two cell types, allowing transfer of multiple infectious events to the T cell. This process allows the virus to avoid neutralization by a class of antibody targeting the gp41 subunit of the envelope glycoproteins. These results have implications for viral spread in vivo and the specificities of neutralizing antibody elicited by antibody-based vaccines.
Author(s): Duncan CJ, Williams JP, Schiffner T, Gartner K, Ochsenbauer C, Kappes J, Russell RA, Frater J, Sattentau QJ
Publication type: Article
Publication status: Published
Journal: Journal of Virology
Print publication date: 03/02/2014
Online publication date: 03/02/2014
Acceptance date: 26/11/2013
ISSN (print): 0022-538X
ISSN (electronic): 1098-5514
Publisher: American Society for Microbiology
PubMed id: 24307588
Altmetrics provided by Altmetric