Abstract
Of the more than 150 human rhinovirus (RV) serotypes, 89 utilize intercellular adhesion molecule-1 (ICAM-1) for cell entry. These belong either to species A or B. We recently demonstrated that RV-B14 and RV-A89, despite binding this same receptor, are routed into distinct endosomal compartments for release of their RNA into the cytosol. To gain insight into the underlying mechanism we now comparatively investigate the port of entry, temperature-dependence of uncoating, and intracellular routing of RV-B3, RV-B14, RV-A16, and RV-A89 in HeLa cells. The effect of various drugs blocking distinct stages on the individual pathways was determined via comparing the number of infected cells in a TissueFaxs instrument. We found that RV-B14 and RV-A89 enter via clathrin-, dynamin-, and cholesterol-dependent pathways, as well as by macropinocytosis. Drugs interfering with actin function similarly blocked entry of all four viruses, indicating their dependence on a dynamic actin network. However, uniquely, RV-A89 was able to produce progeny when internalized at 20 °C followed by neutralizing the endosomal pH and further incubation at 37 °C. Blocking dynein-dependent endosomal transport prevented uncoating of RV-A16 and RV-A89, but not of RV-B3 and RV-B14, indicative for routing of RV-A16 and RV-A89 into the endocytic recycling compartment for uncoating. Our results call for caution when developing drugs aimed at targeting entry or intracellular trafficking of all rhinovirus serotypes.
Highlights
Rhinoviruses (RVs) are the main cause of the common cold
A or B, the latter are exclusively species A [1,2,3]; a more recently discovered species C [4], instead, uses cadherin-related family member 3 (CDHR3), a protein only marginally expressed in established tissue culture cells [5], and neither intercellular adhesion molecule-1 (ICAM-1) nor low-density lipoprotein receptor (LDLR)
Blocking dynein-dependent transport to the minus end of microtubules, we demonstrate that RV-A16 and RV-A89, but not RV-B3 and RV-B14, are routed to the endocytic recycling compartment (ERC)
Summary
Rhinoviruses (RVs) are the main cause of the common cold. Due to the large number of different serotypes (currently about 150 identified) infections are recurrent and, so far, no antiviral drug has reached the market. (89 types) were called the major receptor group and those recognizing the low-density lipoprotein receptor (LDLR) family (12 types) were called the minor receptor group. A or B, the latter are exclusively species A [1,2,3]; a more recently discovered species C [4], instead, uses cadherin-related family member 3 (CDHR3), a protein only marginally expressed in established tissue culture cells [5], and neither ICAM-1 nor LDLR. The minor receptor group species A prototype strain, RV-A2, enters HeLa cells preferentially via clathrin-mediated endocytosis [7] and uncoats in endosomal carrier vesicles (ECV)/late endosomes, a process strictly dependent on acidic pH [8,9]. Blocking dynein-dependent transport to the minus end of microtubules, we demonstrate that RV-A16 and RV-A89, but not RV-B3 and RV-B14, are routed to the ERC
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
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 callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
