The main difference between hemagglutinin and neuraminidase is that hemagglutinin causes red blood cells to agglutinate together, whereas neuraminidase is an exosialidase enzyme that cleaves α-ketosidic linkage between sialic acid and adjacent sugar.
Key Areas Covered
1. What is Hemagglutinin
– Definition, Structure, Function
2. What is Neuraminidase
– Definition, Structure, Function
3. Similarities Between Hemagglutinin and Neuraminidase
– Outline of Common Features
4. Difference Between Hemagglutinin and Neuraminidase
– Comparison of Key Differences
Hemagglutinin, Neuraminidase, Sialidase
What is Hemagglutinin
Hemagglutinin (HA) is a receptor-binding, membrane fusion glycoprotein produced by the influenza A and B viruses. The translation of HA occurs in the form of an uncleaved HA0 precursor protein, and its assembly occurs as a homotrimer in the endoplasmic reticulum. Its transport occurs through the secretory pathway from the endoplasmic reticulum to the plasma membrane. Further, HA0 is cleaved into HA1-HA2 by the protease enzyme of the host. Two domains occur in the mature HA1-HA2 complex. They are the membrane-proximal helix-rich stalk domain and the membrane-distal globular domain, also known as the head. The membrane-proximal helix-rich stalk domain primarily comprises HA2 with a few HA1. In contrast, the membrane-distal globular domain comprises HA1 with a sialic acid (SA) binding pocket.
Furthermore, infection of the influenza A and B viruses initiates with the binding of HA to the SA domains on the host cell’s surface. Also, it triggers the internalization of the viral particles through endocytosis. However, 18 HA subtypes occur in nature with different SA binding pockets.
What is Neuraminidase
Neuraminidase (NA) or sialidase is a glycoside hydrolase that cleaves the glycosidic linkage in neuraminic acid. Structurally, it is a homotetramer embedded in the viral envelope. Each monomer folds into four distinct structural domains: cytoplasmic tail, transmembrane region, catalytic head, and stalk. The cytoplasmic tail shows sequential homology across all influenza A subtypes. It plays a critical role in the transportation and incorporation of neuraminidase. The hydrophobic transmembrane domain occurs in the N-terminus and contains a variable sequence. Also, the stalk region contains considerable variability. The NA tetramers protrude more in the envelope compared to HA trimers. Therefore, it can impact the enzymatic activity and the virulence of NA. Additionally, the catalytic head domain can cleave SA from nearby glycoproteins, preventing the virus trapping.
Moreover, NA is involved in the entry of the influenza virus in two ways: through direct receptor binding and through releasing virions from sialylated ‘decoy’ receptors. They facilitate the viral movement on the cell surface, enabling the access of HA receptors to SA.
Similarities Between Hemagglutinin and Neuraminidase
- Hemagglutinin and neuraminidase are two glycoproteins that occur on the surface of the influenza A and B virus.
- They are viral proteins.
- Both interact with sialic acid.
- They trigger viral entry.
Difference Between Hemagglutinin and Neuraminidase
Hemagglutinin is a group of naturally occurring glycoproteins that cause red blood cells (erythrocytes) to agglutinate or clump together. In contrast, neuraminidase is an exosialidase that cleaves α-ketosidic linkage between the sialic (N-acetylneuraminic) acid and an adjacent sugar residue.
Interaction with the Sialic Acid
Hemagglutinin binds to the sialic acid through the receptor binding sites, triggering viral entry, while neuraminidase is a receptor-destroying enzyme that removes sialic acid.
Hemagglutinin is a homotrimer while neuraminic acid is a homotetramer.
In brief, hemagglutinin and neuraminidase are two glycoproteins that occur in the envelope of influenza A and B viruses. Their main function is to trigger viral entry. Hemagglutinin is a homotrimer that binds to the sialic acid through receptor binding sites. Also, it causes agglutinating of the red blood cells. In comparison, neuraminidase is a homotetramer that destroys the receptors of HA. Therefore, the main difference between hemagglutinin and neuraminidase is their function.
- Du, R.; Cui, Q.; Rong, L. Competitive Cooperation of Hemagglutinin and Neuraminidase during Influenza A Virus Entry. Viruses2019, 11, 458. https://doi.org/10.3390/v11050458
- “CSIRO ScienceImage 354 Influenza Protein Attaching to Cell Membrane” By Health Sciences and Nutrition, CSIRO – Own work (CC-BY 3.0) via Commons Wikimedia
- “Neuraminidase Ribbon Diagram” By NASA – Own Work (Public Domain) via Commons Wikimedia