The key difference between hemagglutinin and neuraminidase is that hemagglutinin binds with cell surface sialic acid on target cells to facilitate viral attachment to host cells while neuraminidase cleaves sialic acid from viral receptors to release the progeny viruses from the host cells.
Influenza A viruses use endocytic machinery to enter host cells. They infect cells by using cellular endocytosis. These viruses attach to the surface of the host cells and increase the assembly of clathrin cargo in order to be internalized by the host cell. Influenza A viruses use two membrane glycoproteins for their infection. They are hemagglutinin (HA) and neuraminidase (NA). Both proteins are critical for virus motility and entry. They participate in viral infectivity, transmissibility, pathogenicity, host specificity, and major antigenicity. Both HA and NA recognize sialic acid on target cells. HA binds with sialic acids and facilitates the attachment of the virus to the host cell surface while NA cleaves sialic acid compounds and facilitates the release of progeny viruses from the host cell.
CONTENTS
1. Overview and Key Difference
2. What is Hemagglutinin
3. What is Neuraminidase
4. Similarities – Hemagglutinin and Neuraminidase
5. Hemagglutinin vs Neuraminidase in Tabular Form
6. Summary – Hemagglutinin vs Neuraminidase
What is Hemagglutinin?
Hemagglutinin is a membrane glycoprotein found on the surface of the Influenza A virus. It is a spiked-shaped protein. It is the major virulence factor of the influenza virus that functions during the early stage of the infection. It binds with the receptors that contain sialic acid compounds of the target cells and initiates the viral attachment with the host cells. Host cells engulf viruses through endocytosis. The viral genome comes into the host cell cytoplasm when the cell digests the content of the endosome. Moreover, hemagglutinin is able to agglutinate red blood cells, compromising the function of RBCs.
Figure 01: Hemagglutinin
Three distinct types of hemagglutinins are important for human infections: H1, H2 and H3. These three types are specific to human influenza. They are specialized to recognize specific sugars in our respiratory tract.
What is Neuraminidase?
Neuraminidase is a surface glycoprotein found in Influenza A virus. It is a mushroom-shaped structure that protrudes from the surface of the virus. It is one of the virulent factors of this virus that helps in overcoming the host barrier.
Figure 02: Neuraminidase
Similar to HA, NA ensures viral infection and transmission from human to human. It works as a hydrolytic enzyme. NA recognizes sialic acid and cleaves it in order to free the virus to infect other new cells. Therefore, NA works during the final stage of the infection. It removes sialic acids from both cellular receptors and from newly synthesized HA and NA. NA action prevents virion aggregation and binding back to the dying host cells. This enables the successful release of viral progeny and spread to new cell targets.
What are the Similarities Between Hemagglutinin and Neuraminidase?
- Hemagglutinin and neuraminidase are two surface glycoproteins that protrude from the Influenza virus outer surface.
- Influenza A virions have these two glycoproteins.
- Virus movement is dependent on both HA and NA.
- Their cooperation enhances virus infection of host cells.
- Viral infectivity, transmissibility, pathogenicity, host specificity, and major antigenicity of Influenza A virus depend on these membrane proteins.
- Both are able to undergo antigenic drift, meaning that they can change their antigenic character.
- HA and NA play a major role in overcoming the host barrier.
- In addition, they are responsible for the efficiency of sustained human-to-human transmission.
What is the Difference Between Hemagglutinin and Neuraminidase?
Hemagglutinin is an antigenic glycoprotein found on the surface of the Influenza A virus that binds with sialic acid-containing cell membrane receptors to initiate viral attachment. In contrast, neuraminidase is an antigenic glycoprotein found on the surface of the Influenza A virus that cleaves sialic acid from receptors to ensure the efficient release of viral progeny. Thus, this is the key difference between hemagglutinin and neuraminidase. Moreover, hemagglutinin is important for the early stage of viral infection, while neuraminidase is important for the final stage of the infection. NA works as a hydrolytic enzyme, while HA cannot work as an enzyme.
The below infographic lists the differences between hemagglutinin and neuraminidase in tabular form for side by side comparison.
Summary – Hemagglutinin vs Neuraminidase
Hemagglutinin and neuraminidase are two major surface glycoproteins found in Influenza A viruses. They are important in viral motility and entry into host cells. Hemagglutinin binds with receptors and facilitates the successful attachment with the host cells. On the other hand, neuraminidase works as a hydrolytic enzyme and cleaves sialic acid from viral receptors in order to release of progeny viruses from the host cells for entry into new cells, initiating a new round of viral replication. So, this summarizes the difference between hemagglutinin and neuraminidase.
Reference:
1. Gamblin, Steven J, and John J Skehel. “Influenza Hemagglutinin and Neuraminidase Membrane Glycoproteins.” The Journal of Biological Chemistry, American Society for Biochemistry and Molecular Biology, 10 Sept. 2010.
2. Sakai, Tatsuya, et al. “Influenza A Virus Hemagglutinin and Neuraminidase Act as Novel Motile Machinery.” Nature News, Nature Publishing Group, 27 Mar. 2017.
Image Courtesy:
1. “Influenza Virus Hemagglutinin (HA) Epitopes on Nanoparticle” By NIAID (CC BY 2.0) via Flickr
2. “Neuraminidasemechanism with without” By Can005 – Own work (CC BY-SA 3.0) via Commons Wikimedia