Cellular transcripts regulated during infections with Highly Pathogenic H5N1 Avian Influenza virus in 3 host systems

Balasubramaniam, Vinod; Hassan, Sharifah Syed; Omar, Abdul Rahman; Mohamed, Maizan; Noor, Suriani Mohd; Mohamed, Ramlan; Othman, Iekhsan

doi:10.1186/1743-422x-8-196

Cited by 11 publications

(14 citation statements)

References 38 publications

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“…Interestingly, the virus dose as well as the duration of infection elevates the expression of actinin‐4, which is consistent with observations showing that viral infection alters the expression of host cell proteins involved in protein synthesis, transcriptional regulation and signaling . The increase in expression of actinin‐4 can be attributed to the transport of NP across the nucleus.…”

Section: Discussionsupporting

confidence: 88%

Influenza A viral nucleoprotein interacts with cytoskeleton scaffolding protein α‐actinin‐4 for viral replication

et al. 2014

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Influenza A virus (IAV), similar to other viruses, exploits the machinery of human host cells for its survival and replication. We identified a-actinin-4, a host cytoskeletal protein, as an interacting partner of IAV nucleoprotein (NP). We confirmed this interaction using co-immunoprecipitation studies, first in a coupled in vitro transcription-translation assay and then in cells either transiently co-expressing the two proteins or infected with whole IAV. Importantly, the NP-actinin-4 interaction was observed in several IAV subtypes, including the 2009 H1N1 pandemic virus. Moreover, immunofluorescence studies revealed that both NP and actinin-4 co-localized largely around the nucleus and also in the cytoplasmic region of virus-infected A549 cells. Silencing of actinin-4 expression resulted in not only a significant decrease in NP, M2 and NS1 viral protein expression, but also a reduction of both NP mRNA and viral RNA levels, as well as viral titers, 24 h post-infection with IAV, suggesting that actinin-4 was critical for viral replication. Furthermore, actinin-4 depletion reduced the amount of NP localized in the nucleus. Treatment of infected cells with wortmannin, a known inhibitor of actinin-4, led to a decrease in NP mRNA levels and also caused the nuclear retention of NP, further strengthening our previous observations. Taken together, the results of the present study indicate that actinin-4, a novel interacting partner of IAV NP, plays a crucial role in viral replication and this interaction may participate in nuclear localization of NP and/or viral ribonucleoproteins.

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Section: Discussionsupporting

confidence: 88%

Influenza A viral nucleoprotein interacts with cytoskeleton scaffolding protein α‐actinin‐4 for viral replication

et al. 2014

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“…A detailed mechanism of how cyclin D3 is targeted to the proteasome complex and which E3-ligase ubiquitylates it will be pursued in future investigations. Down-regulation of the cyclin D3 transcript was previously observed in H5N1-infected cells, but its implication had not been addressed (73). Our study has expanded the repertoire of IAV-M2 host interactors and proposes a novel function of cyclin D3 in the life cycle of IAV.…”

Section: Discussionmentioning

confidence: 72%

Cell Cycle-independent Role of Cyclin D3 in Host Restriction of Influenza Virus Infection

Fan

Mok

Chan

et al. 2017

Journal of Biological Chemistry

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To identify new host factors that modulate the replication of influenza A virus, we performed a yeast two-hybrid screen using the cytoplasmic tail of matrix protein 2 from the highly pathogenic H5N1 strain. The screen revealed a high-score interaction with cyclin D3, a key regulator of cell cycle early G1 phase. M2-cyclin D3 interaction was validated through GST pull-down and recapitulated in influenza A/WSN/33-infected cells. Knockdown of Ccnd3 by small interfering RNA significantly enhanced virus progeny titers in cell culture supernatants. Interestingly, the increase in virus production was due to cyclin D3 deficiency per se and not merely a consequence of cell cycle deregulation. A combined knockdown of Ccnd3 and Rb1, which rescued cell cycle progression into S phase, failed to normalize virus production. Infection by influenza A virus triggered redistribution of cyclin D3 from the nucleus to the cytoplasm, followed by its proteasomal degradation. When overexpressed in HEK 293T cells, cyclin D3 impaired binding of M2 with M1, which is essential for proper assembly of progeny virions, lending further support to its role as a putative restriction factor. Our study describes the identification and characterization of cyclin D3 as a novel interactor of influenza A virus M2 protein. We hypothesize that competitive inhibition of M1-M2 interaction by cyclin D3 impairs infectious virion formation and results in attenuated virus production. In addition, we provide mechanistic insights into the dynamic interplay of influenza virus with the host cell cycle machinery during infection.

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“…The amplified PCR products were separated in 2% agarose gel stained with ethidium bromide. The exact procedure was repeated with all cDNA samples from the three treatment groups and their respective control counterparts using the provided ACPs to amplify the DEGs [20,21,22].…”

Section: Methodsmentioning

confidence: 99%

Identification of Differentially Expressed Genes in BALB/c Mouse Liver upon Primary Infection with DENV1 and Sequential Heterologous Infection with DENV2

et al. 2018

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Dengue virus (DENV) results in 100 million cases of infections and 22,000 deaths per year. Liver involvement, thrombocytopenia, haemorrhage and plasma leakage are characteristic manifestations of severe forms of DENV infection. However, the molecular pathways of DENV infection have not been comprehensively studied compared to the host immunological responses. We performed an in vivo study using the BALB/c mouse model with a modified mRNA differential display methodology (GeneFishingTM) using the annealing control primer (ACP) system to capture differentially expressed genes (DEGs) in mice liver upon primary infection with DENV1 and sequential heterologous infection with DENV2. Secondary heterologous infection with DENV2 was carried out at Immunoglobulin IgM and IgG peaks following the primary DENV1 infection with the hope of determining any potential effect antibodies IgM and IgG may have on sequential heterologous infection. 30 DEGs were identified and sequenced across all three treatment groups and they belong to a variety of important pathways such as apoptosis, innate immune response, inflammatory response, metabolic processes and oxidative stress. Analysis of differentially expressed genes in response to viral infection offers valuable knowledge about the dynamic and complex association between host cell and the virus. Furthermore, some DEGs identified support DENV induced liver damage.

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Cellular transcripts regulated during infections with Highly Pathogenic H5N1 Avian Influenza virus in 3 host systems

Cited by 11 publications

References 38 publications

Influenza A viral nucleoprotein interacts with cytoskeleton scaffolding protein α‐actinin‐4 for viral replication

Influenza A viral nucleoprotein interacts with cytoskeleton scaffolding protein α‐actinin‐4 for viral replication

Cell Cycle-independent Role of Cyclin D3 in Host Restriction of Influenza Virus Infection

Identification of Differentially Expressed Genes in BALB/c Mouse Liver upon Primary Infection with DENV1 and Sequential Heterologous Infection with DENV2

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