Antibodies to PB1-F2 protein are induced in response to influenza A virus infection

Krejnusová, Ingrid; Gocníková, Hana; Bystrická, M; Blaskovicová, H; Poláková, K; Yewdell, Jonathan W.; Bennink, Jack R.; Russ, G

doi:10.1007/s00705-009-0479-5

Cited by 26 publications

(19 citation statements)

References 23 publications

(20 reference statements)

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“…This is consistent with the previous finding that a delay in viral clearance rather than a high initial viral load in the respiratory tract is associated with severe disease (37,38). Antibodies against PB1-F2 and M1 can be detected in patients with influenza virus infection, but the functional significance of these antibodies is unknown (20,52). Other potential effects of nonneutralizing antibody include the activation of the complement cascade and antibody-dependent cellular cytotoxicity, which can be protective or detrimental if excessively proinflammatory (1,27).…”

Section: Discussionsupporting

confidence: 91%

High Titer and Avidity of Nonneutralizing Antibodies against Influenza Vaccine Antigen Are Associated with Severe Influenza

Zhang

Hung

et al. 2012

Clin. Vaccine Immunol.

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ABSTRACTThe importance of neutralizing antibody in protection against influenza virus is well established, but the role of the early antibody response during the initial stage of infection in affecting the severity of disease is unknown. The 2009 influenza pandemic provided a unique opportunity for study because most patients lacked preexisting neutralizing antibody. In this study, we compared the antibody responses of 52 patients with severe or mild disease, using sera collected at admission. A microneutralization (MN) assay was used to detect neutralizing antibody. We also developed an enzyme-linked immunosorbent assay (ELISA) which detects both neutralizing and nonneutralizing antibodies against viral antigens from a split-virion inactivated monovalent influenza virus vaccine. While the MN titers were not significantly different between the two groups (P= 0.764), the ELISA titer and ELISA/MN titer ratio were significantly higher for patients with severe disease than for those with mild disease (P= 0.004 andP= 0.011, respectively). This finding suggested that in patients with severe disease, a larger proportion of serum antibodies were antibodies with no detectable neutralizing activity. The antibody avidity was also significantly higher in patients with severe disease than in those with mild disease (P< 0.05). Among patients with severe disease, those who required positive pressure ventilation (PPV) had significantly higher ELISA titers than those who did not require PPV (P< 0.05). Multivariate analysis showed that the ELISA titer and antibody avidity were independently associated with severe disease. Higher titers of nonneutralizing antibody with higher avidity at the early stage of influenza virus infection may be associated with worse clinical severity and poorer outcomes.

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Section: Discussionsupporting

confidence: 91%

High Titer and Avidity of Nonneutralizing Antibodies against Influenza Vaccine Antigen Are Associated with Severe Influenza

Zhang

Hung

et al. 2012

Clin. Vaccine Immunol.

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“…As a loading control, the detection of the β-actin was used by the mouse anti-β-actin monoclonal antibody (Sigma Aldrich). Monoclonal antibody (MAb) AG55 anti-PB1-F2 (Krejnusová et al, 2009) and MAb 107 anti-NP (Varečková et al, 1995) were prepared by the standard hybridoma procedure. MAb M21 anti-M1 and MAb NS1 anti-NS1 were kindly provided by John Yewdell, Bethesda, NIH.…”

Section: Cells and Viruses Madin-darby Canine Kidney Cells (Mdck)mentioning

confidence: 99%

N-terminal region of the PB1-F2 protein is responsible for increased expression of influenza A viral protein PB1

Košík¹,

Krejnusová²,

Bystrická³

et al. 2011

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Summary. -Influenza A virus (IAV) PB1-F2 protein is encoded by an alternative reading frame (+1) within the PB1 gene. PB1-F2 has been shown to contribute to the pathogenesis of influenza virus infection as well as to the secondary bacterial infection. More recently has been shown that PB1-F2 protein may regulate a viral RNA (vRNA) polymerase activity by the interaction with PB1 protein. We proved that PB1-F2 protein increased the level of expression of PB1 protein and vRNA in the infected cells. Moreover, we demonstrated that a higher level of vRNA expression resulted in the increase of expression of multiple viral proteins, including NP, M1, and NS1. Finally, we used plasmids expressing N-terminal (1-50 aa) or C-terminal (51-87 aa) region of the PB1-F2 molecule for transfection of MDCK cells co-infected with influenza A/Puerto Rico/8/34 (H1N1) virus deficient in the PB1-F2 protein expression (PR8ΔPB1-F2). These experiments clearly showed that N-terminal region of PB1-F2 protein was responsible for the increase in PB1 protein expression. C-terminal region of PB1-F2 protein had no effect. Thus, we have identified the important function for N-terminal region of PB1-F2 protein.

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“…We assume that the PB1 ORF, driven by a strong CMV promoter, led in our experiments to high expression and release of free PB1, which was responsible for induction of antibodies and cell damage. Although the PB1 plasmid contained a complete PB1-F2 ORF [11] and anti-PB1-F2 antibodies are induced after infection [12,13], we could not detect antibodies to Fig. 1 Analysis of specific serum antibodies in mice immunized with DNA vaccines by ELISA.…”

Section: Pb1 Dna Vaccine Induces Humoral Antibodies In Micementioning

confidence: 87%

A DNA vaccine expressing PB1 protein of influenza A virus protects mice against virus infection

et al. 2012

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Although influenza DNA vaccine research has focused mainly on viral hemagglutinin and has led to promising results, other virion proteins have also shown some protective potential. In this work, we explored the potential of a DNA vaccine based on the PB1 protein to protect BALB/c mice against lethal influenza A virus infection. The DNA vaccine consisted of pTriEx4 plasmid expressing PB1. As a positive control, a pTriEx4 plasmid expressing influenza A virus HA was used. Two weeks after three subcutaneous doses of DNA vaccine, the mice were challenged intranasally with 1 LD50 of A/Puerto Rico/8/34 (H1N1) virus, and PB1- and HA-specific antibodies, survival rate, body weight change, viral mRNA load, infectious virus titer in the lungs, cytokines IL-2, IL-4 and IL-10, and granzyme-B were measured. The results showed that (i) the PB1-expressing DNA vaccine provided a fair protective immunity in the mouse model and (ii) viral structural proteins such as PB1 represent promising antigens for DNA vaccination against influenza A.

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Antibodies to PB1-F2 protein are induced in response to influenza A virus infection

Cited by 26 publications

References 23 publications

High Titer and Avidity of Nonneutralizing Antibodies against Influenza Vaccine Antigen Are Associated with Severe Influenza

High Titer and Avidity of Nonneutralizing Antibodies against Influenza Vaccine Antigen Are Associated with Severe Influenza

N-terminal region of the PB1-F2 protein is responsible for increased expression of influenza A viral protein PB1

A DNA vaccine expressing PB1 protein of influenza A virus protects mice against virus infection

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