Ebolavirus
Ebolavirus cycle
Macropinocytic protusions engulf non specifically portions of the external environment through an actin-dependent machanism
GP mRNA is co-transcriptionally edited by stuttering, thereby encoding sGP and GP.
smal GP is a dimer secreted out of the cell and reduces acquired immune response. This protein may act as a decoy against antibodies or immune cells.
Viral RNA-dependent RNA polymerase transcribes the viral genes from the minus strand RNA template.
Viral RNA-dependent RNA polymerase replicates the genome in host cytoplasm
Vp24 inhibits nuclear entry mechanism involving non common Nuclear localization Signals
Ebolavirus virion can attach to host DC-SIGN or L-SIGN. Host HAVCR1(TIM1) binds phosphatidylserine (PS) exposed on virion membrane, triggering a intracellular signal that leads to macropinocytosis.
Fusion of viral with cellular membrane is triggered in macropinosome. It's induced by processing of viral GP that interacts with host NPC1. In some cells low pH could trigger the fusion
Virion budding occurs at the plasma membrane, and virions can receive several copies of ebola genome.
VP35 interacts with host IKKepsilon, thereby preventing host antiviral defense activation by viral RNA pattern recognition.
Vp24 inhibits host Interferon signaling, thereby switching off antiviral defenses activated by external cell signaling.
Binds and sequesters virus-neutralizing antibodies directed against surface GP, also would would act as a viral cytokine to modulate immune response
REPLICATION
CYTOPLASMIC
- Attachment to host receptors through GP glycoprotein like DC-SIGN and DC-SIGNR
. - Cellular receptor like HAVCR1(TIM1) binds phosphatidyl serine on virion membrane and a signal is transduced into the cell that trigger the macropinocytosis program.
- The virion enters the cell by Macropinocytosis. In some culture cells, GP glycoprotein can be processed by host Cathepsin L and Cathepsin B into 19kDa GP1. But this processing is not happening in all cells or for all ebolavirus.
- GP1 interacts with host NPC1, in late macropinosome and promotes Fusion of virus membrane with the vesicle membrane. The ribonucleocapsid is then released into the cytoplasm.
- Sequential transcription, viral mRNAs are capped and polyadenylated by polymerase stuttering in the cytoplasm.
- Replication presumably starts when enough nucleoprotein is present to encapsidate neo-synthetized antigenomes and genomes.
- The ribonucleocapsid interacts with the matrix protein, and buds via the host ESCRT complexes from the plasma membrane, releasing the virion .
A new player in the puzzle of filovirus entry
Judith M. White, Kathryn L. Schornberg
Nat. Rev. Microbiol. May 2012; 10: 317?322
Judith M. White, Kathryn L. Schornberg
Nat. Rev. Microbiol. May 2012; 10: 317?322
C-type lectins DC-SIGN and L-SIGN mediate cellular entry by Ebola virus in cis and in trans
Carmen P. Alvarez, F?tima Lasala, Jaime Carrillo, Oscar Mu?iz, Angel L. Corb?, Rafael Delgado
J. Virol. July 2002; 76: 6841?6844
Carmen P. Alvarez, F?tima Lasala, Jaime Carrillo, Oscar Mu?iz, Angel L. Corb?, Rafael Delgado
J. Virol. July 2002; 76: 6841?6844
Ebola virus entry requires the host?programmed recognition of an intracellular receptor
Emily Happy Miller, Gregor Obernosterer, Matthijs Raaben, Andrew S. Herbert, Maika S. Deffieu, Anuja Krishnan, Esther Ndungo, Rohini G. Sandesara, Jan E. Carette, Ana I. Kuehne, Gordon Ruthel, Suzanne R. Pfeffer, John M. Dye, Sean P. Whelan, Thijn R. Brummelkamp, Kartik Chandran
The EMBO Journal April 18, 2012; 31: 1947?1960
Emily Happy Miller, Gregor Obernosterer, Matthijs Raaben, Andrew S. Herbert, Maika S. Deffieu, Anuja Krishnan, Esther Ndungo, Rohini G. Sandesara, Jan E. Carette, Ana I. Kuehne, Gordon Ruthel, Suzanne R. Pfeffer, John M. Dye, Sean P. Whelan, Thijn R. Brummelkamp, Kartik Chandran
The EMBO Journal April 18, 2012; 31: 1947?1960
Ebolavirus is internalized into host cells via macropinocytosis in a viral glycoprotein-dependent manner
Asuka Nanbo, Masaki Imai, Shinji Watanabe, Takeshi Noda, Kei Takahashi, Gabriele Neumann, Peter Halfmann, Yoshihiro Kawaoka
PLoS Pathog. 2010; 6: e1001121
Asuka Nanbo, Masaki Imai, Shinji Watanabe, Takeshi Noda, Kei Takahashi, Gabriele Neumann, Peter Halfmann, Yoshihiro Kawaoka
PLoS Pathog. 2010; 6: e1001121
The Tyro3 receptor kinase Axl enhances macropinocytosis of Zaire ebolavirus
Catherine L. Hunt, Andrey A. Kolokoltsov, Robert A. Davey, Wendy Maury
J. Virol. January 2011; 85: 334?347
Catherine L. Hunt, Andrey A. Kolokoltsov, Robert A. Davey, Wendy Maury
J. Virol. January 2011; 85: 334?347
Cathepsin B & L are not required for ebola virus replication
Andrea Marzi, Thomas Reinheckel, Heinz Feldmann
PLoS Negl Trop Dis 2012; 6: e1923
Andrea Marzi, Thomas Reinheckel, Heinz Feldmann
PLoS Negl Trop Dis 2012; 6: e1923
A PPxY motif within the VP40 protein of Ebola virus interacts physically and functionally with a ubiquitin ligase: implications for filovirus budding
R. N. Harty, M. E. Brown, G. Wang, J. Huibregtse, F. P. Hayes
Proc. Natl. Acad. Sci. U.S.A. December 5, 2000; 97: 13871?13876
R. N. Harty, M. E. Brown, G. Wang, J. Huibregtse, F. P. Hayes
Proc. Natl. Acad. Sci. U.S.A. December 5, 2000; 97: 13871?13876
Overlapping motifs (PTAP and PPEY) within the Ebola virus VP40 protein function independently as late budding domains: involvement of host proteins TSG101 and VPS-4
Jillian M. Licata, Martha Simpson-Holley, Nathan T. Wright, Ziying Han, Jason Paragas, Ronald N. Harty
J. Virol. February 2003; 77: 1812?1819
Jillian M. Licata, Martha Simpson-Holley, Nathan T. Wright, Ziying Han, Jason Paragas, Ronald N. Harty
J. Virol. February 2003; 77: 1812?1819