Matches in SemOpenAlex for { <https://semopenalex.org/work/W4300688752> ?p ?o ?g. }
- W4300688752 endingPage "e1010892" @default.
- W4300688752 startingPage "e1010892" @default.
- W4300688752 abstract "Many viruses encode ion channel proteins that oligomerize to form hydrophilic pores in membranes of virus-infected cells and the viral membrane in some enveloped viruses. Alphavirus 6K, human immunodeficiency virus type 1 Vpu (HIV-Vpu), influenza A virus M2 (IAV-M2), and hepatitis C virus P7 (HCV-P7) are transmembrane ion channel proteins that play essential roles in virus assembly, budding, and entry. While the oligomeric structures and mechanisms of ion channel activity are well-established for M2 and P7, these remain unknown for 6K. Here we investigated the functional role of the ion channel activity of 6K in alphavirus assembly by utilizing a series of Sindbis virus (SINV) ion channel chimeras expressing the ion channel helix from Vpu or M2 or substituting the entire 6K protein with full-length P7, in cis. We demonstrate that the Vpu helix efficiently complements 6K, whereas M2 and P7 are less efficient. Our results indicate that while SINV is primarily insensitive to the M2 ion channel inhibitor amantadine, the Vpu inhibitor 5-N, N-Hexamethylene amiloride (HMA), significantly reduces SINV release, suggesting that the ion channel activity of 6K similar to Vpu, promotes virus budding. Using live-cell imaging of SINV with a miniSOG-tagged 6K and mCherry-tagged E2, we further demonstrate that 6K and E2 colocalize with the Golgi apparatus in the secretory pathway. To contextualize the localization of 6K in the Golgi, we analyzed cells infected with SINV and SINV-ion channel chimeras using transmission electron microscopy. Our results provide evidence for the first time for the functional role of 6K in type II cytopathic vacuoles (CPV-II) formation. We demonstrate that in the absence of 6K, CPV-II, which originates from the Golgi apparatus, is not detected in infected cells, with a concomitant reduction in the glycoprotein transport to the plasma membrane. Substituting a functional ion channel, M2 or Vpu localizing to Golgi, restores CPV-II production, whereas P7, retained in the ER, is inadequate to induce CPV-II formation. Altogether our results indicate that ion channel activity of 6K is required for the formation of CPV-II from the Golgi apparatus, promoting glycoprotein spike transport to the plasma membrane and efficient virus budding." @default.
- W4300688752 created "2022-10-04" @default.
- W4300688752 creator A5041207856 @default.
- W4300688752 creator A5068627678 @default.
- W4300688752 creator A5069864999 @default.
- W4300688752 creator A5081482416 @default.
- W4300688752 date "2022-10-03" @default.
- W4300688752 modified "2023-10-01" @default.
- W4300688752 title "Requirement of a functional ion channel for Sindbis virus glycoprotein transport, CPV-II formation, and efficient virus budding" @default.
- W4300688752 cites W1518668585 @default.
- W4300688752 cites W1532985146 @default.
- W4300688752 cites W1558513743 @default.
- W4300688752 cites W1585610099 @default.
- W4300688752 cites W1607273785 @default.
- W4300688752 cites W1657414671 @default.
- W4300688752 cites W1665760694 @default.
- W4300688752 cites W1764270605 @default.
- W4300688752 cites W1855484651 @default.
- W4300688752 cites W1966153332 @default.
- W4300688752 cites W1966734154 @default.
- W4300688752 cites W1967322800 @default.
- W4300688752 cites W1970408170 @default.
- W4300688752 cites W1976867329 @default.
- W4300688752 cites W1986002459 @default.
- W4300688752 cites W1987459045 @default.
- W4300688752 cites W1988708890 @default.
- W4300688752 cites W1995097201 @default.
- W4300688752 cites W2009516769 @default.
- W4300688752 cites W2010315691 @default.
- W4300688752 cites W2010317967 @default.
- W4300688752 cites W2010458160 @default.
- W4300688752 cites W2013878893 @default.
- W4300688752 cites W2015121618 @default.
- W4300688752 cites W2020769855 @default.
- W4300688752 cites W2030412425 @default.
- W4300688752 cites W2032452247 @default.
- W4300688752 cites W2032457529 @default.
- W4300688752 cites W2036270340 @default.
- W4300688752 cites W2037831301 @default.
- W4300688752 cites W2039438672 @default.
- W4300688752 cites W2048147848 @default.
- W4300688752 cites W2049676886 @default.
- W4300688752 cites W2050997685 @default.
- W4300688752 cites W2051535361 @default.
- W4300688752 cites W2062135212 @default.
- W4300688752 cites W2064396919 @default.
- W4300688752 cites W2066891535 @default.
- W4300688752 cites W2068385155 @default.
- W4300688752 cites W2070524991 @default.
- W4300688752 cites W2070721147 @default.
- W4300688752 cites W2070979531 @default.
- W4300688752 cites W2073517039 @default.
- W4300688752 cites W2074975548 @default.
- W4300688752 cites W2075824896 @default.
- W4300688752 cites W2076109789 @default.
- W4300688752 cites W2076694007 @default.
- W4300688752 cites W2087087296 @default.
- W4300688752 cites W2087485595 @default.
- W4300688752 cites W2089415411 @default.
- W4300688752 cites W2097905379 @default.
- W4300688752 cites W2099769915 @default.
- W4300688752 cites W2100214164 @default.
- W4300688752 cites W2100759967 @default.
- W4300688752 cites W2101666840 @default.
- W4300688752 cites W2104217772 @default.
- W4300688752 cites W2105291981 @default.
- W4300688752 cites W2107026123 @default.
- W4300688752 cites W2108558787 @default.
- W4300688752 cites W2108730380 @default.
- W4300688752 cites W2111212265 @default.
- W4300688752 cites W2117256797 @default.
- W4300688752 cites W2118620546 @default.
- W4300688752 cites W2120159282 @default.
- W4300688752 cites W2120519511 @default.
- W4300688752 cites W2120772351 @default.
- W4300688752 cites W2123799993 @default.
- W4300688752 cites W2130560148 @default.
- W4300688752 cites W2131061583 @default.
- W4300688752 cites W2131854840 @default.
- W4300688752 cites W2133712091 @default.
- W4300688752 cites W2138743794 @default.
- W4300688752 cites W2139596364 @default.
- W4300688752 cites W2141918346 @default.
- W4300688752 cites W2148910155 @default.
- W4300688752 cites W2152854377 @default.
- W4300688752 cites W2156661615 @default.
- W4300688752 cites W2167660970 @default.
- W4300688752 cites W2172895128 @default.
- W4300688752 cites W2198233536 @default.
- W4300688752 cites W2216999854 @default.
- W4300688752 cites W2233751927 @default.
- W4300688752 cites W2272536236 @default.
- W4300688752 cites W2344746490 @default.
- W4300688752 cites W2355112196 @default.
- W4300688752 cites W2493667413 @default.
- W4300688752 cites W2556782307 @default.
- W4300688752 cites W2584729109 @default.
- W4300688752 cites W2588207450 @default.