Magic™ Mouse Anti-Adenovirus monoclonal antibody, clone 2F464

Adenoviruses are viruses that belong to the Adenoviridae family and are distinguished by being able to enter almost any host cell (from respiratory, gut and eye) including the eye. They are not enveloped, ie without a lipid bilayer, but instead have their own protein capsid that confers toughness in the environment. Adenoviruses are ubiquitous germs that infect humans with everything from a strep throat infection to the severer conjunctivitis and gastroenteritis. Because of adenoviruses' ability to attack many tissues and remain persistent in the environment, they have been centrally studied in both medicine and biotechnology. Adenoviruses can be very sophisticated in their infection and pathogenicity for their minuscule genome, making them a novel and interesting target for virology and gene therapy.

Figure 1. Adenovirus infection and replication pathway. (Sources: Mary Miu Yee Waye, et al. 2010)

There are different serotypes of adenoviruses, and at least 50 of them have been found that can be transmitted to humans. These serotypes are further divided according to their capacity to enter particular tissues and their tendency to induce particular clinical signs. Adenovirus serotype 1, for instance, has caused respiratory illnesses like the common cold; types 4 and 7 have caused serious respiratory illnesses like pneumonia. Instead, serotypes 8, 19 and 37 have been associated with eye infections such as conjunctivitis or "pink eye". Strangely, adenoviruses can also cause gastroenteritis and have even been known to be involved in some cases of acute hemorrhagic cystitis, bladder inflammation. That diverse repertoire of infections comes partly because adenoviruses attach to all sorts of cells via a wide array of surface receptors, infecting and mutating in all sorts of tissues in the body. Adenoviruses are not just unusual in that they are so broadly infectious – but also because they could be used in medicine and gene therapy. In recent decades, scientists have taken to adenoviruses because of their capacity to introduce genomes into the host cell. It's made them one of the most popular vectors in gene therapy, particularly for genetic disorders like cystic fibrosis, hemophilia and certain cancers. Adenoviruses are not integrated into the host genome, which prevents insertional mutagenesis and genetic harm from occurring in other viral vectors. That attribute and the fact that they're extremely effective at both infecting dividing and non-dividing cells has made adenoviral vectors a go-to vector for gene transfer. But for all their promise, adenovirus therapies are not completely relegable to the clinic. Immune immunity to adenoviruses – especially established immunity in patients who have been exposed to the virus earlier in life – can limit the efficacy of such treatments and keep them from spreading. Adenoviruses are rather large viruses that have a very specific structure that makes them resilient and stable in the environment. The viral capsid – made of more than 200 protein subunits – is icosahedra, defending the viral genome from the outside world. Unlike enveloped viruses that can become ill from temperature and desiccation, adenoviruses persist long-term in environments that contain detergents and high temperatures. Their durability is also why they are extremely hard to neutralize in the environment and remain active on surfaces and transmit between people. The virus has special proteins on its surface, too, that make it bind to the host cells and trigger infection. The most vital of these is the fibre protein, which extends from each tip of the icosahedral capsid. The fibre protein binds to specific receptors on the surface of host cells and then opens the door to the virus.

Beyond gene therapy, there are other biotech uses for adenoviruses. They've been used to generate recombinant proteins (eg, vaccines) using the virus to release foreign DNA into the host cell. They've even produced vaccines for a range of illnesses, such as the COVID-19 vaccines that are made with adenovirus. Then there are adenoviruses, which have been used to study the activity of genes, proteins and cell mechanisms, because they can efficiently deliver genes into cells. Infectious disease can be made to have genes of interest that researchers modify in the viral genome, then study how those genes function in cells and in disease. Adenoviruses are still among the most research-intensive viral vectors in clinical practice for gene therapy and vaccine development. They have a huge host repertoire and are efficient infecting dividing and non-dividing cells making them a great candidate for gene delivery in several therapeutic situations. But they are not unproblematic to deploy. The immune response to adenoviruses (at least, for people who already have immunity) remains a huge obstacle to their clinical potential. Also, while adenoviral vectors deliver genes very efficiently, they don't insert themselves into the host genome, so the therapeutic effect can be temporary. In order to address these issues, there is now research underway to build new adenoviral vectors that are immunogenic at a low level, efficient at delivering genes, and stable for extended therapy. And the creation of adenovirus vaccines was another major focus, especially against new infectious diseases. Successfully exploiting adenovirus vaccines for infectious diseases like COVID-19 have made them very useful for mass vaccine production and delivery. Such vaccines use a modified version of adenoviruses to transmit viral antigens to the body and cause the immune system to fight infection. As the world battles new infectious diseases, adenoviral vaccines will be key to the international health struggle.

Adenovirus vector
AdV
Adenovirus Group
Adenoviral Vector