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. 2008 Jun 6;4(6):e1000085.
doi: 10.1371/journal.ppat.1000085.

Cellular proteins in influenza virus particles

Affiliations

Cellular proteins in influenza virus particles

Megan L Shaw et al. PLoS Pathog. .

Abstract

Virions are thought to contain all the essential proteins that govern virus egress from the host cell and initiation of replication in the target cell. It has been known for some time that influenza virions contain nine viral proteins; however, analyses of other enveloped viruses have revealed that proteins from the host cell can also be detected in virions. To address whether the same is true for influenza virus, we used two complementary mass spectrometry approaches to perform a comprehensive proteomic analysis of purified influenza virus particles. In addition to the aforementioned nine virus-encoded proteins, we detected the presence of 36 host-encoded proteins. These include both cytoplasmic and membrane-bound proteins that can be grouped into several functional categories, such as cytoskeletal proteins, annexins, glycolytic enzymes, and tetraspanins. Interestingly, a significant number of these have also been reported to be present in virions of other virus families. Protease treatment of virions combined with immunoblot analysis was used to verify the presence of the cellular protein and also to determine whether it is located in the core of the influenza virus particle. Immunogold labeling confirmed the presence of membrane-bound host proteins on the influenza virus envelope. The identification of cellular constituents of influenza virions has important implications for understanding the interactions of influenza virus with its host and brings us a step closer to defining the cellular requirements for influenza virus replication. While not all of the host proteins are necessarily incorporated specifically, those that are and are found to have an essential role represent novel targets for antiviral drugs and for attenuation of viruses for vaccine purposes.

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Conflict of interest statement

The authors have declared that no competing interests exist.

Figures

Figure 1
Figure 1. Analysis of purified influenza virus preparations.
(A) Electron micrograph of negatively stained, sucrose gradient purified influenza A/WSN/33 virus at 50,000× magnification. (B) SDS-PAGE separation of proteins in a purified influenza virus preparation. 15 ug of untreated (lane 1) or deglycosylated (lane 2) proteins were separated on an 8–16% polyacrylamide gel and stained with Coomassie blue. The positions of the viral proteins, identified by their predicted molecular weights, are indicated.
Figure 2
Figure 2. Confirmation of host protein incorporation into influenza virions derived from different cell lines.
Influenza A/WSN/33 virus was purified from the supernatant of infected A549 and Vero cells. 2 ug of purified virus derived from A549 and Vero cells (lane 1 and 2, respectively) and 10 ug of cellular extracts from uninfected A549 and Vero cells (lanes 3 and 4, respectively) were subjected to western blot analysis with antibodies against the following proteins: (A) Influenza hemagglutinin (HA0 and HA1 are visible), (B) Beta actin, (C) Annexin A5, (D) Cyclophilin A. Numbers to the left are molecular weight markers.
Figure 3
Figure 3. The effect of protease treatment on influenza virion associated host proteins.
Purified influenza A/WSN/33 virus was either mock treated or subjected to overnight digestion with subtilisin followed by concentration through a sucrose cushion. 10 ug of mock infected cell lysate (lane 1) or influenza infected cell lysate (lane 2) and 2 ug of untreated influenza virions (lane 3) or protease treated influenza virions (lane 4) were then analyzed by western blot with antibodies against the indicated proteins. Numbers to the right are molecular weight markers.
Figure 4
Figure 4. Gradient fractionation demonstrates co-purification of influenza virus and CD9.
Influenza A/WSN/33 virus was purified over (A) sucrose and (B) Optiprep gradients. Fractions were taken from the top and analyzed by western blot for the presence of NP, CD9 and MHC-I, as indicated. Numbers to the right are molecular weight markers.
Figure 5
Figure 5. Immunogold labeling of host proteins in purified influenza virions.
Influenza virions purified from the supernatant of infected Vero cells were immunogold labeled with antibodies against (A) Hemagglutinin, (B) CD9, (C) CD81 and (D) normal mouse IgG. Labeled virus was negatively stained with sodium silicotungstate and visualized by electron microscopy (50,000× magnification). The number of gold particles per virion is shown below (n = the number of virions counted).

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