Coxsackievirus A16 utilizes cell surface heparan sulfate glycosaminoglycans as its attachment receptor

Xueyang Zhang1, Jinping Shi1, Xiaohua Ye1

  • 1Unit of Vaccinology &Antiviral Strategies, CAS Key Laboratory of Molecular Virology &Immunology, Institut Pasteur of Shanghai, Chinese Academy of Sciences, Shanghai 200031, China.

Insights

Coxsackievirus A16 (CVA16) uses heparan sulfate as an attachment receptor for hand, foot, and mouth disease. Specific viral capsid residues, particularly R166, are crucial for this interaction and viral entry.

Area of Science:

  • Virology
  • Molecular Biology
  • Biochemistry

Background:

  • Coxsackievirus A16 (CVA16) causes hand, foot, and mouth disease, a prevalent childhood illness in the Asia-Pacific region.
  • Scavenger receptor B2 is a known CVA16 receptor involved in viral uncoating.
  • The initial attachment receptor for CVA16 remained unidentified.

Purpose of the Study:

  • To identify the attachment receptor for Coxsackievirus A16.
  • To elucidate the role of viral capsid proteins in CVA16 attachment.
  • To provide insights for developing CVA16 antiviral strategies.

Main Methods:

  • Cell-based assays to assess viral attachment.
  • Site-directed mutagenesis of CVA16 capsid proteins.
  • Heparan sulfate binding assays.
  • Analysis of viral infectivity.

Main Results:

  • CVA16 utilizes surface heparan sulfate glycosaminoglycans for cellular attachment.
  • Five positively charged residues at the virion's five-fold vertex are critical for heparan sulfate binding.
  • Mutation of arginine 166 (R166) to alanine (R166A) significantly impaired heparan sulfate binding and viral attachment.

Conclusions:

  • Heparan sulfate acts as a primary attachment receptor for CVA16.
  • Specific residues on the CVA16 capsid mediate interaction with heparan sulfate.
  • Understanding these early infection events can guide the development of novel CVA16 therapeutics and vaccines.

Related Concept Videos

Glycocalyx and its Functions01:14

Glycocalyx and its Functions

The glycocalyx is a carbohydrate-rich, fuzzy-appearing layer on the outer surface of the cell membrane. It is highly hydrophilic, because of this it attracts large amounts of water to the cell's surface. This aids the cell's interaction with the watery environment and also helps it to obtain substances dissolved in the water. It is also important for cell identification, self/non-self determination, and embryonic development and is used in cell-to-cell attachments to form tissues.
9.5K
Immunoglobulin-like Cell Adhesion Molecules01:31

Immunoglobulin-like Cell Adhesion Molecules

Immunoglobulin-like cell adhesion molecules or Ig-CAMs are a versatile group of cell surface glycoproteins belonging to the immunoglobulin protein superfamily. Ig-CAMs possess the characteristic immunoglobulin protein domains and other domains such as the fibronectin type III domain. The Ig domains are glycosylated to varying degrees in different Ig-CAMs.
Ig-CAMs exhibit either homophilic binding (to other Ig-CAMs) or heterophilic binding (to other ligands such as integrins). While most Ig-CAMs...
4.5K
Glycosaminoglycans01:23

Glycosaminoglycans

Glycosaminoglycans (GAGs), also known as mucopolysaccharides, are long and linear polymers comprising of specific repeating disaccharides - the amino sugar that can be N-acetylglucosamine or N-acetylgalactosamine, and a uronic acid that is usually glucuronic acid or iduronic acid.
GAGS are found in the extracellular matrix of vertebrates, invertebrates, and bacteria. Due to their polar nature they attract water, and serve as excellent lubricants or shock absorbers in an animal body.
Hyaluronic...
7.3K
Surface Membrane Barriers01:18

Surface Membrane Barriers

The skin and mucous membranes serve as the primary line of defense against pathogens by providing both physical and chemical protection. These barriers are essential in preventing the entry and establishment of microbes, thereby maintaining the integrity of the host.
The outer layer of the skin, the epidermis, is a robust barrier comprising layers of closely packed keratinized cells. This dense arrangement prevents microbes from penetrating the body. The periodic shedding of epidermal cells...
3.1K
Antigen Presenting Cells01:22

Antigen Presenting Cells

The immune system is a complex network of cells and molecules that protects the body from foreign invaders. T cells, a type of white blood cell, play a crucial role in this process. They recognize and attack foreign substances, such as pathogens, that enter the body.
T cells require the help of antigen-presenting cells (APCs), which process foreign antigens into smaller fragments that can be recognized by T cells. These APCs are highly specialized cells that efficiently internalize antigens...
3.8K
Cell Adhesion Molecules - Types and Functions01:20

Cell Adhesion Molecules - Types and Functions

Cell adhesion molecules (CAMs) are pivotal to multicellularity and the coordinated functioning of tissues and organ systems. They enable physical interactions between cells and provide mechanical strength to tissues. They also function as receptors for signal transmission across the plasma membrane. The CAMs are broadly classified into four families - integrins, cadherins, selectins, and immunoglobulin-like CAMs (IgCAMs).
CAM Families
The Integrin family of proteins is primarily  involved...
10.2K