Alteration of the basic amino acid domain of wild-type matrix protein reduced influenza virus replication at non-permissive temperature

2004 ◽  
Vol 1263 ◽  
pp. 83-89
Author(s):  
Teresa Liu ◽  
Zhiping Ye
Keyword(s):  
Influenza Virus ◽  
Amino Acid ◽  
Virus Replication ◽  
Matrix Protein ◽  
Basic Amino Acid ◽  
Permissive Temperature ◽  
Wild Type ◽  
Influenza Virus Replication ◽  
Acid Domain ◽  
Amino Acid Domain

scholarly journals G Protein Pathway Suppressor 1 Promotes Influenza Virus Polymerase Activity by Activating the NF-κB Signaling Pathway

mBio ◽  
2019 ◽  
Vol 10 (6) ◽  
Author(s):  
Tomoko Kuwahara ◽  
Seiya Yamayoshi ◽  
Takeshi Noda ◽  
Yoshihiro Kawaoka
Keyword(s):  
Influenza Virus ◽  
Signaling Pathway ◽  
G Protein ◽  
Virus Replication ◽  
Matrix Protein ◽  
Polymerase Activity ◽  
Host Protein ◽  
Host Cells ◽  
Dependent Manner ◽  
Influenza Virus Replication

ABSTRACT Influenza virus relies heavily on cellular machinery to replicate in host cells. Therefore, to better understand the influenza virus life cycle, it is important to identify which host proteins are involved and how they function in virus replication. Previously, we identified G protein pathway suppressor 1 (GPS1) to be a matrix protein 2 (M2)-interacting host protein. GPS1 is a component of the COP9 signalosome, which regulates the NF-κB signaling pathway. Here, we found that the downregulation of GPS1 expression reduced influenza virus replication by more than 2 log units. Although GPS1 was not involved in the early and late stages of virus replication, such as viral entry, uncoating, assembly, or budding, we found that viral polymerase activity was impaired in GPS1-downregulated cells. Moreover, our results suggest that M2 activates the NF-κB signaling pathway in a GPS1-dependent manner and that activation of NF-κB signaling leads to the upregulation of influenza virus polymerase activity. Our findings indicate that GPS1 is involved in the transcription and replication of influenza virus genomic RNA through the activation of the NF-κB signaling pathway. IMPORTANCE In the present study, we identified G protein pathway suppressor 1 (GPS1) to be a host cellular protein that is important for influenza virus replication. We also found that GPS1 plays a role in viral genome transcription through the NF-κB signaling pathway. Moreover, downregulation of GPS1 also affected the growth of vesicular stomatitis virus. Therefore, GPS1 may be a host target for antiviral drugs against influenza virus and possibly other viruses.

scholarly journals Delivery of bFGF for Tissue Engineering by Tethering to the ECM

2015 ◽  
Vol 2015 ◽  
pp. 1-6 ◽  
Author(s):  
Chawapun Suttinont ◽  
Yasumasa Mashimo ◽  
Masayasu Mie ◽  
Eiry Kobatake
Keyword(s):  
Tissue Engineering ◽  
Extracellular Matrix ◽  
Amino Acid ◽  
Growth Factor ◽  
Functional Unit ◽  
Basic Amino Acid ◽  
Target Cells ◽  
C Terminus ◽  
Acid Domain ◽  
Amino Acid Domain

Delivery of growth factors to target cells is an important subject in tissue engineering. Towards that end, we have developed a growth factor-tethered extracellular matrix (ECM). Here, basic fibroblast growth factor (bFGF) was tethered to extracellular matrix noncovalently. The designed ECM was comprised of 12 repeats of the APGVGV peptide motif derived from elastin as a stable structural unit and included the well-known cell adhesive RGD peptide as an active functional unit. To bind bFGF to the ECM, an acidic amino acid-rich sequence was introduced at the C-terminus of the ECM protein. It consisted of 5 repeats of 4 aspartic acids and a serine, DDDDS. bFGF has a highly basic amino acid domain. Therefore, bFGF was tethered to the ECM protein by electrostatic interaction. Cells cultured on bFGF-tethered ECM were well attached to the ECM and induced proliferation without addition of soluble bFGF.

scholarly journals YRKL Sequence of Influenza Virus M1 Functions as the L Domain Motif and Interacts with VPS28 and Cdc42

2006 ◽  
Vol 80 (5) ◽  
pp. 2291-2308 ◽  
Author(s):  
Eric Ka-Wai Hui ◽  
Subrata Barman ◽  
Dominic Ho-Ping Tang ◽  
Bryan France ◽  
Debi P. Nayak
Keyword(s):  
Influenza Virus ◽  
Virus Replication ◽  
Influenza A ◽  
Matrix Protein ◽  
Virus Titer ◽  
Virus Production ◽  
Dominant Negative ◽  
Virus Budding ◽  
M1 Protein ◽  
Influenza Virus Replication

ABSTRACT Earlier studies have shown that the C-terminal half of helix 6 (H6) of the influenza A virus matrix protein (M1) containing the YRKL sequence is involved in virus budding (E. K.-W. Hui, S. Barman, T. Y. Yang, and D. P. Nayak, J. Virol. 77:7078-7092, 2003). In this report, we show that the YRKL sequence is the L domain motif of influenza virus. Like other L domains, YRKL can be inserted at different locations on the mutant M1 protein and can restore virus budding in a position-independent manner. Although YRKL is a part of the nuclear localization signal (NLS), the function of YRKL was independent of the NLS activity and the NLS function of M1 was not required for influenza virus replication. Some mutations in YRKL and the adjacent region caused a reduction in the virus titer by blocking virus release, and some affected virus morphology, producing elongated particles. Coimmunoprecipitation and Western blotting analyses showed that VPS28, a component of the ESCRT-I complex, and Cdc42, a member of the Rho family GTP-binding proteins, interacted with the M1 protein via the YRKL motif. In addition, depletion of VPS28 and Cdc42 by small interfering RNA resulted in reduction of influenza virus production. Moreover, overexpression of dominant-negative Cdc42 inhibited influenza virus replication, whereas a constitutively active Cdc42 mutant enhanced virus production in infected cells. These results indicated that VPS28, a component of ESCRT-I, and Cdc42, a small G protein, are associated with the M1 protein and involved in the influenza virus life cycle.

scholarly journals A natural variant in ANP32B impairs influenza virus replication in human cells

2021 ◽  
Vol 102 (9) ◽  
Author(s):  
Ecco Staller ◽  
Carol M. Sheppard ◽  
Laury Baillon ◽  
Rebecca Frise ◽  
Thomas P. Peacock ◽  
...  
Keyword(s):  
Influenza Virus ◽  
Virus Replication ◽  
Human Cells ◽  
Influenza Viruses ◽  
Dominant Negative ◽  
Dominant Negative Effect ◽  
Wild Type ◽  
Single Nucleotide Variants ◽  
Natural Variant ◽  
Influenza Virus Replication

Viruses require host factors to support their replication, and genetic variation in such factors can affect susceptibility to infectious disease. Influenza virus replication in human cells relies on ANP32 proteins, which are involved in assembly of replication-competent dimeric influenza virus polymerase (FluPol) complexes. Here, we investigate naturally occurring single nucleotide variants (SNV) in the human Anp32A and Anp32B genes. We note that variant rs182096718 in Anp32B is found at a higher frequency than other variants in either gene. This SNV results in a D130A substitution in ANP32B, which is less able to support FluPol activity than wild-type ANP32B and binds FluPol with lower affinity. Interestingly, ANP32B-D130A exerts a dominant negative effect over wild-type ANP32B and interferes with the functionally redundant paralogue ANP32A. FluPol activity and virus replication are attenuated in CRISPR-edited cells expressing wild-type ANP32A and mutant ANP32B-D130A. We propose a model in which the D130A mutation impairs FluPol dimer formation, thus resulting in compromised replication. We suggest that both homozygous and heterozygous carriers of rs182096718 may have some genetic protection against influenza viruses.

scholarly journals Targeting Cell Division Cycle 25 Homolog B To Regulate Influenza Virus Replication

2013 ◽  
Vol 87 (24) ◽  
pp. 13775-13784 ◽  
Author(s):  
O. Perwitasari ◽  
A. C. Torrecilhas ◽  
X. Yan ◽  
S. Johnson ◽  
C. White ◽  
...  
Keyword(s):  
Influenza Virus ◽  
Cell Division ◽  
Virus Replication ◽  
Cell Division Cycle ◽  
Influenza Virus Replication
Sign in / Sign up

Export Citation Format

Share Document