Myosin motors on the pathway of viral infections.

Molecular motors are microscopic machines that use energy from adenosine triphosphate (ATP) hydrolysis to generate movement. While kinesins and dynein are molecular motors associated with microtubule tracks, myosins bind to and move on actin filaments. Mammalian cells express several myosin motors. They power cellular processes such as endo- and exocytosis, intracellular trafficking, transcription, migration, and cytokinesis. As viruses navigate through cells, they may take advantage or be hindered by host components and machinery, including the cytoskeleton. This review delves into myosins' cell roles and compares them to their reported functions in viral infections. In most cases, the previously described myosin functions align with their reported role in viral infections, although not in all cases. This opens the possibility that knowledge obtained from studying myosins in viral infections might shed light on new physiological roles for myosins in cells. However, given the high number of myosins expressed and the variety of viruses investigated in the different studies, it is challenging to infer whether the interactions found are specific to a single virus or can be applied to other viruses with the same characteristics. We conclude that the participation of myosins in viral cycles is still a largely unexplored area, especially concerning unconventional myosins.

Flagellin/NLRC4 Pathway Rescues NLRP3-Inflammasome Defect in Dendritic Cells From HIV-Infected Patients: Perspective for New Adjuvant in Immunocompromised Individuals.

Introduction: NLRP3 inflammasome plays a key role in dendritic cells (DC) activation in response to vaccine adjuvants, however we previously showed that it is not properly activated in DC from HIV-infected patients (HIV-DC), explaining, at least in part, the poor response to immunization of these patients. Taking in account that several cytoplasmic receptors are able to activate inflammasome, and that bacterial components are considered as a novel and efficient adjuvant, we postulated that bacterial flagellin (FLG), a natural ligand of NAIP/NLRC4 inflammasome, could rescue the activation of the complex in HIV-DC. Objective: Demonstrate that FLG is able to activate monocyte-derived dendritic cells from HIV-infected individuals better than LPS, and to what extent the entity of inflammasome activation differs between DC from HIV-infected patients and healthy donors. Methods: Monocyte-derived dendritic cells from HIV-infected patients (HIV-DC) and healthy donors (HD-DC) were stimulated with FLG, and inflammasome as well as DC activation (phenotypic profile, cytokine production, autologous lymphocytes activation) were compared. Chemical and genetic inhibitors were used to depict the relative contribution of NLRC4 and NLRP3 in HIV/HD-DC response to FLG. Results: FLG properly activates HD-DC and HIV-DC. FLG induces higher inflammasome activation than LPS in HIV-DC. FLG acts through NLRC4 and NLRP3 in HD-DC, but at a lesser extent in HIV-DC due to intrinsic NLRP3 defect. Conclusions: FLG by-passes NLRP3 defect in HIV-DC, through the activation of NAIP/NLRC4 inflammasome, indicating possible future use of the bacterial component as an efficient adjuvant in immunocompromised individuals.

HIV trafficking in host cells: motors wanted!

Throughout the viral replication cycle, viral proteins, complexes, and particles need to be transported within host cells. These transport events are dependent on the host cell cytoskeleton and molecular motors. However, the mechanisms by which virus is trafficked along cytoskeleton filaments and how molecular motors are recruited and regulated to guarantee successful integration of the viral genome and production of new viruses has only recently begun to be understood. Recent studies on HIV have identified specific molecular motors involved in the trafficking of these viral particles. Here we review recent literature on the transport of HIV components in the cell, provide evidence for the identity and role of molecular motors in this process, and highlight how these trafficking events may be related to those occurring with other viruses.

Critical role for the kinesin KIF3A in the HIV life cycle in primary human macrophages.

Macrophages are long-lived target cells for HIV infection and are considered viral reservoirs. HIV assembly in macrophages occurs in virus-containing compartments (VCCs) in which virions accumulate and are stored. The regulation of the trafficking and release of these VCCs remains unknown. Using high resolution light and electron microscopy of HIV-1-infected primary human macrophages, we show that the spatial distribution of VCCs depended on the microtubule network and that VCC-limiting membrane was closely associated with KIF3A+ microtubules. Silencing KIF3A strongly decreased virus release from HIV-1-infected macrophages, leading to VCC accumulation intracellularly. Time-lapse microscopy further suggested that VCCs and associated KIF3A move together along microtubules. Importantly, KIF3A does not play a role in HIV release from T cells that do not possess VCCs. These results reveal that HIV-1 requires the molecular motor KIF3 to complete its cycle in primary macrophages. Targeting this step may lead to novel strategies to eliminate this viral reservoir.