Tuesday, February 4, 2020

The Biology of the Coronavirus

The global spread of viral pneumonia associated with the so-called “Wuhan coronavirus” appears to be reaching pandemic proportions. Given this distressing reality, it is important to more fully understand the biology of this virus.

Viruses represent a class of infectious agents that pose interesting challenges as witnessed by the HIV/AIDS virus that is the causative agent of the devastating acquired immunodeficiency syndrome (AIDS) that targets a particularly important cell type in the human adaptive immune system – the so-called, “T-helper cells (CD4).” Viruses possess the unusual property of being inert when outside a living cell. However, once they gain access to a living cell, the infective agent – either ribonucleic acid (RNA) or deoxyribonucleic acid (DNA) - commandeers the host cellular machinery to make copies of itself. This process can lead either to the ultimate death of the target cell or can result in a transformation of the host DNA that in some instances can lead to cancer – T-cell leukemia (HTLV-1 virus) and Cervical cancer (Human Papilloma virus – HPV) being some important examples.

Coronaviruses are a family of enveloped, single-stranded, positive-strand RNA viruses that are classified within the Nidovirales order. The name coronavirus was coined on account of the corona-like appearance of this virus as viewed under the electron microscope (See accompanying image). The existence of this type of virus was first reported in 1949 and the molecular mechanisms of both replication and disease formation was well-studied in the 1970s. The coronavirus family comprises pathogens that infect many animal species. Coronaviruses have been shown to be the causative agents for acute and chronic respiratory, enteric and central nervous system (CNS) diseases. This family of viruses have been associated with infectious disease in mouse (murine), a pig (porcine) transmissible gastroenteritis (TGEV), cow (bovine) and a bird (avian) bronchitis (BCoV). The first example of a potentially life-threatening human emerging coronavirus was the acute respiratory syndrome coronavirus (SARS-CoV).

Until 2003 the human coronavirus was only known to produce cold-like symptoms. This changed with the onset of severe acute respiratory syndrome (SARS) and now the Wuhan coronavirus that is apparently spread readily from human to human. These kinds of changes in infectivity are not unusual in the evolution of a virus; since, the infective material is prone to mutation. It is for this reason that it has proven exceedingly difficult to come up with an effective vaccine against HIV/AIDS.

Structurally, a virus particle consists of a protein outer coat that interacts and fuses with the cell membrane of the host cell. This is generally followed by the transfer of the infective agent – in this case the RNA of the coronavirus. Once this RNA enters the host cell, it directs the replication of its viral RNA and interferes with host cell processes. These tasks are accomplished through the transcription of viral RNA into proteins that exploit the cell’s protein synthesis “machinery.” It seems that coronavirus contains 7 genes – each gene having the blueprints for the production of a unique protein. One of the products of these genes is the so-called “spike” protein that plays a role in attaching to the host cell and has been shown to play a major part in the virus’ pathogenicity. The end result of this process is the formation of multiple copies of the virus followed by the death of the host cell and subsequent release of the new viruses into the extra-cellular environment.

The global nature of this threat can be circumvented by a number of different approaches - the first being isolating infected individuals and thereby thwarting the spread of the disease to others. It is likely that the virus is spread through aerosols as a result of coughing from infected individuals. This standard epidemiological approach is made particularly difficult given the reality of the constant movement of people to all areas of the globe.

However, it is also imperative that research efforts be directed towards developing a vaccine in order to assist the human immune system in its attempt to destroy the coronavirus once it has gained entry into the host. In regard to SARS, several studies were directed towards the development of active immunization strategies. These included Inactivated virions, recombinant antigen, DNA vaccines, and adenoviral vectors as well as other avenues of research. Undoubtedly, these kinds of studies will continue with added urgency.