MX is supported by a grant from the China Scholarship Council

MX is supported by a grant from the China Scholarship Council. infection by HIV-1 in infected hosts is still a matter of debate. Using multiphoton intravital microscopy in HIV-1-infected humanized mice, Murooka et al. showed that HIV-1-infected T Eribulin Mesylate cells establish interaction with surrounding cells and can even form syncytia with other lymph node-resident cells. The potency of infected T cells in lymph nodes to migrate may facilitate virus cell-to-cell transmission and spreading (12). Interestingly, exposure of human or macaque mucosal explants to HIV-1- or SIV-infected cells, allows more efficient viral transmission and infection than cell-free viruses (13, 14), suggesting the potency of HIV-1- or SIV-infected T cells to transmit viruses and propagate infection in host tissues. The high efficiency of cell-to-cell infection was also proposed to be a mechanism for HIV-1 to escape to antiretroviral therapy and neutralizing antibodies (15) but these results are still controversial and will be discussed below (4, 6, 16). Different modes of infection through different cellular structures enabling close contacts between virus-donor cells and recipient target cells have been described over the past years for cell-to-cell transmission of HIV-1 (18, 19) and (20C22), and play important roles in the transmission of information between cells from different physiological systems, such as neurons (18, 23, 24), myeloid cells (25C29), or T cells (30). Among the described membrane protrusions, two different types of nanotubes have been reported, corresponding to close-ended nanotubes and open-ended nanotubes (also known as TNTs) (27, 31, 32). Intercellular communications involving TNTs were first observed in 2004 as F-actin-containing membrane extensions able to connect distant cells during minutes to hours (18). TNTs are fragile and dynamic structures extended up to 100?m in length with diameters ranging from 50 to Eribulin Mesylate 200?nm, and are not attached to the substratum (18, 30). They can mediate and facilitate the transfer, between several cell types, of cytoplasmic, and plasma membrane molecules, Ca2+ (29, 33), cargos including vesicles derived from various organelles such as early endosomes, endoplasmic reticulum, Golgi complex, and lysosomes (24, 33, 34), and even bigger cellular organelles like mitochondria and endosome-related structures (18, 32), but also pathogens such as bacteria (28). Several studies showed that HIV-1 utilizes TNT networks Eribulin Mesylate to move from one cell to another leading to virus cell-to-cell transfer (25, 30, 34, 35) (Figure ?(Figure1A).1A). The frequency of TNT formation is not affected by HIV-1 in T cells but these structures could allow rapid spread of virus between T cells (30). Virus particles can thus be transferred by surfing along the surface of TNTs between T cells (30). Virus dissemination through TNTs was also reported between macrophages, in which HIV-1 particles can be transferred through intracellular vesicles derived Eribulin Mesylate from the endosomal reticulum or the Golgi apparatus (34, 35). Furthermore, in macrophages, HIV-1 increases the number of these intercellular structures to infect new cells (25). The Eribulin Mesylate HIV-1 Nef auxiliary protein has been reported to be responsible for the formation of TNTs in the THP-1 macrophage-like cell line (36) as well as in primary monocyte-derived macrophages, in which Nef alters the localization of the scaffolding protein M-Sec (37), which is a key regulator of TNT formation by a still undefined mechanism (26). Open up in another screen Amount 1 Intercellular procedures and buildings involved with cell-to-cell transmitting of HIV-1. (ACG) Plans represent the various pathways for HIV-1 cell-to-cell transfer between donor cells (in green) and focus on cells (in red). Another path of viral cell-to-cell transmitting through membrane expansion involving development of filopodia continues to be first defined for transmission from the retroviral murine leukemia trojan (MLV) (19). Filopodia are F-actin-rich CDCA8 slim plasma membrane extensions that get excited about several cellular features, such as for example chemo-migration, adhesion towards the extracellular matrix, or development.