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Identification and characterization of host proteins inducing the endoplasmic reticulum invagination during Flavivirus infection

Tran, Pham Tue Hung, 1991- (author)
Örebro universitet,Institutionen för medicinska vetenskaper,Molecular Flavirus group
Asghar, Naveed, 1983- (author)
Örebro universitet,Institutionen för medicinska vetenskaper
Karlsson, Roger (author)
Department ofClinical Microbiology, Sahlgrenska University Hospital, Gothenburg, Sweden; NanoxisConsulting AB, Gothenburg, Sweden
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Karlsson, Anders (author)
Department ofClinical Microbiology, Sahlgrenska University Hospital, Gothenburg, Sweden; NanoxisConsulting AB, Gothenburg, Sweden
Johansson, Magnus, 1969- (author)
Örebro universitet,Institutionen för medicinska vetenskaper
Melik, Wessam, 1973- (author)
Örebro universitet,Institutionen för medicinska vetenskaper
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 (creator_code:org_t)
2019
2019
English.
In: Positive-Strand RNA Viuses. ; , s. 280-280
  • Conference paper (peer-reviewed)
Abstract Subject headings
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  • When Flaviviruses infect host cells, they can induce invagination of endoplasmic reticulum (ER) membrane to form vesicle-like compartments. These unique structures are hypothetical to facilitate the viral replication by reducing diffusion of virus replication machinery and viral RNA, providing a scaffold to anchor the replication complex, and protecting viral RNA from host cell intrinsic surveillance. The rearrangements of ER membrane to form these replication compartments (RCs) require modifications in its lipid constituents or binding of proteins to the membrane. Flaviviruses, indeed, use their proteins to generate RCs. It has been implicated that both KUNV and DENV viral NS1, NS2A, NS4A, NS4B proteins could induce membrane remodelings. However, it is recondite whether host proteins can also participate in the formation and maintenance of RCs.In this project, we aimed to identify and characterize of host proteins inducing RC generation during Flavivirus infections. We used A549 as a cell model, and mosquito-borne Zika and Kunjin virus, and tick-borne Langat virus as virus models. After virus infections, ER membranes were harvested using ultracentrifuge with a sucrose gradient. Proteins from these ERs were identified using mass spectrometry. We compared the differences between the ER proteomes of infected cells and non-infected cells to identify host candidate proteins that can cause the RC formation.  We are attempting to enrich the RC-containing fractions and identifying proteins here, which narrows the list of true candidate proteins. The candidate proteins then will be characterized by using molecular techniques such as gene knock down, overexpression, and microscopy techniques.

Subject headings

MEDICIN OCH HÄLSOVETENSKAP  -- Klinisk medicin -- Infektionsmedicin (hsv//swe)
MEDICAL AND HEALTH SCIENCES  -- Clinical Medicine -- Infectious Medicine (hsv//eng)

Keyword

Replication complex
Kunjin
Langat
Zika
Molekylär cellbiologi
Molecular Cellbiology
Biomedicin
Biomedicine
Infektionssjukdomar
Infectious Diseases

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