Both influenza virus and (IFV), and Measles Virus (MV) are enveloped viruses with class I
fusion glycoproteins. Experimental exposure to low pH (5.5) buffer will inactivate IFV, but not
MV. Based on this information, What can you infer about the entry pathways and mechanism of
two viruses?
Solution
Entry of virus in the host membrane includes a number of steps.
The entry pathway of Influenza virus is influenced by a fusion protein termed as hemagglutinin.
It is a trimeric glycoprotien present in multiple copies in the membrane envelope of influenza
virus. The structure of hemagglutinin contains a receptor binding sites, fusion peptide, a
metastable structure motif, and the transmembrane domain.
For the entry of IFV the first step involves the recognition of the host cell receptor molecules ,
terminal sialic acid by hemagglutinin. The attachment is multivalent in nature as the multiple
copies of trimetric hemagglutinin gets attached with the receptors on the membrane and triggers
endocytosis of the IFV. The virus is trapped in endosome and moves via a unidirectional
pathway towards nucleus of the host cell. At this position the pH of the endosome become acidic
and induces a dramatic conformational change in hemagglutinin to insert the fusion protein into
the host membrane (nucleus). It induces a juxtaposition of the two membrane and forms a fusion
pore that allows the release of the genome segment in the of the IFV. The genome then
undergoes translation in host cells and thus develop protein and in turns shows symptoms of
disease.
At low pH the hemagglutinin of IFV undergoes a conformational change which results in
exposure of a hydrophobic segment of the molecule which is crucial to expression of viral fusion
activity and thus inactivate the entry of the virus. For optimal expression of fusion activity the
virus must bound to the target membrane before exposure to low pH.
In case of measles virus (MV), like other paramyxoviruses (those which have single stand RNA
which are used as template for mRNA synthesis), for the fusion both the fusion protein (F) and
hemagglutinin (H) are required. These proteins are found on the viral surface in a regular array
of tightly packed spikes H tetramers and F timers. H proteins recognizes the receptors on the
target membrane as well as help the F protein in the fusion process which involves the insertion
of hydrophobic fusion peptide in the cell membrane. Unlike IFV, MV uses single protein , the
regulator of complement activation CD46 as its main receptors. CD46 is a type 1 transmembrane
protein which is expressed in four isoform. MV enters a cell by pH independent membrane
fusion at the cell surface. Binding of the H protein is believed to induce conformational change
of the H protein as well as that of the F proteins. The hydrophobic fusion peptide inside the F
protein is then exposed and inserted into the plasma membrane of the target cell. The structural
changes of the F protein then induce fusion of vir.
Both influenza virus and (IFV), and Measles Virus (MV) are enveloped.pdf
1. Both influenza virus and (IFV), and Measles Virus (MV) are enveloped viruses with class I
fusion glycoproteins. Experimental exposure to low pH (5.5) buffer will inactivate IFV, but not
MV. Based on this information, What can you infer about the entry pathways and mechanism of
two viruses?
Solution
Entry of virus in the host membrane includes a number of steps.
The entry pathway of Influenza virus is influenced by a fusion protein termed as hemagglutinin.
It is a trimeric glycoprotien present in multiple copies in the membrane envelope of influenza
virus. The structure of hemagglutinin contains a receptor binding sites, fusion peptide, a
metastable structure motif, and the transmembrane domain.
For the entry of IFV the first step involves the recognition of the host cell receptor molecules ,
terminal sialic acid by hemagglutinin. The attachment is multivalent in nature as the multiple
copies of trimetric hemagglutinin gets attached with the receptors on the membrane and triggers
endocytosis of the IFV. The virus is trapped in endosome and moves via a unidirectional
pathway towards nucleus of the host cell. At this position the pH of the endosome become acidic
and induces a dramatic conformational change in hemagglutinin to insert the fusion protein into
the host membrane (nucleus). It induces a juxtaposition of the two membrane and forms a fusion
pore that allows the release of the genome segment in the of the IFV. The genome then
undergoes translation in host cells and thus develop protein and in turns shows symptoms of
disease.
At low pH the hemagglutinin of IFV undergoes a conformational change which results in
exposure of a hydrophobic segment of the molecule which is crucial to expression of viral fusion
activity and thus inactivate the entry of the virus. For optimal expression of fusion activity the
virus must bound to the target membrane before exposure to low pH.
In case of measles virus (MV), like other paramyxoviruses (those which have single stand RNA
which are used as template for mRNA synthesis), for the fusion both the fusion protein (F) and
hemagglutinin (H) are required. These proteins are found on the viral surface in a regular array
of tightly packed spikes H tetramers and F timers. H proteins recognizes the receptors on the
target membrane as well as help the F protein in the fusion process which involves the insertion
of hydrophobic fusion peptide in the cell membrane. Unlike IFV, MV uses single protein , the
regulator of complement activation CD46 as its main receptors. CD46 is a type 1 transmembrane
protein which is expressed in four isoform. MV enters a cell by pH independent membrane
fusion at the cell surface. Binding of the H protein is believed to induce conformational change
2. of the H protein as well as that of the F proteins. The hydrophobic fusion peptide inside the F
protein is then exposed and inserted into the plasma membrane of the target cell. The structural
changes of the F protein then induce fusion of viral envelope with the host membrane. Infection
of the susceptible cells, causes cell-cell fusion, producing multinucleated giant cells, the typical
cytopathic effect of MV infection.
