What is Enterovirus D68?
Picture this: It’s the 1940s, and virologists are intensely studying Poliovirus, a notorious virus that was causing a crippling disease called Polio; during its peak, paralyzing or killing over half a million people worldwide, especially affecting children.
Much effort was being made to grow the polio virus in labs, which is crucial to having enough virus for research. Scientists needed a large quantity of the virus to develop vaccines and treatments. It was a race to save lives and prevent the spread of Polio.
But this work had a secondary result. It kick-started the discovery of other members of this family of viruses. The Enterovirus genus was named, and its members were classified due to their tropism for the human alimentary tract. Species members include:
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- Enterovirus A (e.g., Coxsackievirus A71),
- Enterovirus B (e.g., Coxsackievirus B3),
- Rhinovirus A, B or C,
- Enterovirus C (e.g., Poliovirus),
- and Enterovirus D (e.g., EV-D68).
Enterovirus D68 (EV-D68) is a member of the Picornaviridae family and is classified in the genus Enterovirus. EV-D68 is somewhat unusual. It shares much with its relatives, Poliovirus and Rhinovirus. But while Poliovirus and Rhinovirus sometimes show up in our blood (viremia), EV-D68 doesn’t.
What are the symptoms?
EV-D68 infection might cause no symptoms or only produce the typical signs of a runny nose, sneezing, coughing, and muscle aches.
But there’s a darker side to EV-D68. It can cause serious respiratory problems, making breathing a challenge with wheezing and discomfort.
Now, here’s where things get serious. EV-D68 can also lead to a condition known as acute flaccid myelitis, where your muscles go weak and your reflexes slow; it can be especially tough for children. They might struggle to hold their heads up and even have trouble swallowing.
Recovering from acute flaccid myelitis isn’t easy. It’s a tough fight against the virus, and many children don’t ever fully regain their normal function. In rare cases, some children can become quadriplegic.
Mode of Transmission: Respiratory Route
Just remember, EV-D68 is a respiratory virus, and it spreads through respiratory droplets. So, if someone’s got it, watch out for saliva, nasal mucus, or sputum.
Why is Enterovirus D68 important?
Enterovirus D68 was first isolated in 1962, but for various reasons, it failed to attract much research attention. As a result, until quite recently, we had limited knowledge about this pathogen, from laboratory studies to clinical insights.
However, starting in the early 2000s and continuing through to the present day, there has been a surge in reported cases and outbreaks of infections, especially among children. These infections have caused significant morbidity, raising concerns within the medical community.
This upturn in cases is unsettling: EV-D68 can cause acute flaccid myelitis – a condition resembling the acute flaccid paralysis caused by Polio. But unlike Polio, there is no vaccine or specific antiviral treatment available for EV-D68.
This combination of factors has prompted some experts to question whether EV-D68 has the potential to become the new Polio. The situation is raising important questions about the virus and its implications for public health.
What is Enterovirus D68 composed of?
EV-D68 belongs to the Picornaviridae family, which is characterised by viruses with a single-stranded positive-sense RNA genome and a non-enveloped icosahedral protein capsid.
In simpler terms, these viruses have their genetic material wrapped up in a protective protein shell that has a specific shape called an icosahedron (imagine a 20-sided dice, all faces equilateral triangles). This shell doesn’t have a layer of fat around it like some other viruses do.
Thus, EV-D68 is classified as a non-enveloped virus, although this may not be as clear cut as first believed, which is discussed in more detail below.
How does Enterovirus D68 infect cells and replicate?
To infect a cell, Enteroviruses need to find a way in. They do this by binding to specific receptors on the cell’s surface and then slipping inside through a process called endocytosis.
Enterovirus D68 (EV-D68) can attach itself to the α2-6-linked sialic acid receptor, which is found on cell surfaces of the upper respiratory tract. But that’s not the only way it gets in. We know that α2-6-linked sialic acid is not the only receptor for D68 because soluble sialic acid does not inhibit infection (if α2-6-linked sialic acid was EV-D68’s only route into cells, the soluble sialic acid could competitively bind to α2-6-linked sialic acid and block infection).
Also, it’s important to mention that EV-D68 can infect various cell types, including nerve cells and other cell types, both in laboratory settings (in vitro) and in living organisms (in vivo). So, the receptor remains enigmatic; we’re still working on how exactly this virus finds its way into our cells.
EV-D68 and Its Resemblance to Human Rhinoviruses
EV-D68 is acid-sensitive, meaning it needs a low pH to reorganise its capsid to form a pore through the endosomal membrane through which it can enter and infect cells. Also, EV-D68 has an optimum replication temperature of 33°C (internal body cells are normally at 37°C).
This lower replication temperature, acid lability, and replication in the respiratory tract are characteristics that EV-D68 shares with human Rhinoviruses. Polio is different in that it replicates in the throat and in the intestines. Therefore, it is no surprise that EV-D68 was first known as Rhinovirus 87.
However, advances in genetics and phylogeny (comparing evolution) analyses have since shown that EV-D68 is a closer relative to Enteroviruses. This makes EV-D68 unique among Enterovirus – all other Enterovirus transmit via the oral-faecal route, while Rhinoviruses are respiratory viruses.
Enveloped or non-enveloped
Some interesting studies have recently shed light on how picornavirus replicates within and then infects its target cells. After viral genome RNA replication, Enteroviruses assemble in the cell’s cytoplasm. However, it has been shown that these viruses can also undergo maturation within a specialised intracellular structure, the autophagosome, which can house multiple viral particles simultaneously. Once mature, these viral particles can exit the cell through either cell lysis or exocytosis of these autophagosome compartments.
These non-enveloped viruses, enclosed within a membrane compartment, may exhibit greater infectivity compared to their ‘normal’ counterparts. The autophagosome membrane encasing the virions has been proposed to protect the virions. Protection has been inferred from work with Poliovirus, which passes through the intestinal tract, although EV-D68 has been shown to be within these structures and manipulate the cellular machinery to do so (Chen et al. 2015; Corona et al. 2018).
These recent findings raise intriguing questions about whether these studies might offer insights into the ‘non-neutralisable fraction’ often observed in early Enterovirus antibody neutralisation assays. However, it’s essential to recognise that this area blurs the lines between enveloped and non-enveloped virus classifications. This distinction has the potential to significantly impact the design and effectiveness of treatments, making it an exciting area of research warranting further investigation.
What can VRS do?
VRS can test your neutralising antibodies, antiviral compounds, virucidal solutions/suspensions, antiviral fabrics, or materials against Enterovirus D68. Contact us today, and one of our virologists will get back to you promptly.
Blog by Scott Lawrence
Edited by Reckon Better – Science Communication Services
Edited by Reckon Better – Science Communication Services
