KIF13A mediates influenza a virus ribonucleoproteins trafficking

Abstract

Influenza A is a rapidly evolving virus that is successful in provoking periodic epidemics and occasional pandemics in humans. Viral assembly is complex as the virus incorporates an eight-partite genome of RNA (in the form of viral ribonucleoproteins, vRNPs), and viral genome assembly - with its implications to public health - is not completely understood. It has previously been reported that vRNPs are transported to the cell surface on Rab11-containing vesicles by using microtubules but, so far, no molecular motor has been assigned to the process. Here, we have identified KIF13A, a member of the kinesin-3 family, as the first molecular motor to efficiently transport vRNP-Rab11 vesicles during infection with influenza A. Depletion of KIF13A resulted in reduced viral titers and less accumulation of vRNPs at the cell surface, without interfering with the levels of other viral proteins at sites of viral assembly. In addition, when overexpressed and following two separate approaches to displace vRNP-Rab11 vesicles, KIF13A increased levels of vRNP at the plasma membrane. Together, our results show that KIF13A plays an important role in the transport of influenza A vRNPs, a crucial step for viral assembly.This article has an associated First Person interview with the first author of the paper.

Quantitative live cell imaging reveals influenza virus manipulation of Rab11A transport through reduced dynein association

“…However, further studies are needed to clarify this hypothesis. In addition, lack of direct interaction between KIF13A and Rab11A in A549 cells suggests that dynein dysregulation and not KIF13A, as previously suggested 53 , may be responsible for disrupting Rab11A intracellular movement during IAV infection.…”

“…FIP2 is thought to mediate association with myosin 5 20 , which was not altered in our pulldown analysis ( Supplementary Data 1). Interestingly, it has also been reported that Rab11A-RE bound to IAV vRNP uses KIF13A to travel to budding regions on the cell plasma membrane 53 . However, in agreement with Ramos-Nascimento et al who were unable to observe direct association of KIF13A with Rab11A, we did not detect KIF13A in our Rab11A pull-down mass spectrometry analysis.…”

“…12). Previous data implicating KIF13A in Rab11A transport were derived mainly from the percentage of NP signal found within 2 μm from the cell periphery of static images from a confocal slice 53 . However, our results reveal a robust disruption in the amounts of dynein associated with Rab11A during IAV infection, suggesting that IAV infection alters the stoichiometry of Rab11A-RE-associated motors by reducing association of minus-end directed dynein motors.…”

Influenza A Virus Ribonucleoproteins Form Liquid Organelles at Endoplasmic Reticulum Exit Sites

“…2). In addition, IAV Rab11/vRNPs hotspots were shown to exhibit heterogeneous movements, as if moving on actin or sliding on microtubules 10,17 ,30 , using molecular motors 65 . However, it was recently reported that, in the absence of intact microtubules, vRNAs could be transported through the cytoplasm independently of Rab11-GTP 66 and a candidate that was recently proposed was the ER 16 .…”

Lnc-EPB41-Protein Interactions Associated with Congenital Pouch Colon

“…As the lncRNAs play a role in regulation [ 18 ], there is an enormous scope for ascertaining lncRNA-protein interactions. In this study, we inferred a lncRNA, viz.lnc-EPB41-1-1promiscuously interacting with six protein-coding genes and established its interaction with KIF13A, a 202 kDa trafficking protein [ 19 ] and a bona fide gene causal to CPC [ 3 ]. Furthermore, this kinesin family of microtubule-based motor proteins is known to regulate various processes such as mannose-6-phosphate receptor (M6PR) transport besides mediating melanosome biogenesis and cytokinesis.…”