Are the viruses causing infectious diseases in humans are entirely new, and they didn?t exist in the past? Or the viruses always coexisted with us, and suddenly started infecting humans? Rather viral infectious diseases were occurring in humans in some parts of the world, but global travel and media exposure made you connect with it?
COVID-19 pandemic caused by the SARS-CoV2 claiming 162 956 human lives and affected the global population in almost all the aspects of life, in effect, the world stood frozen.
The Ebola virus disease outbreak (EVD) in the Democratic Republic of Congo, the world’s second-largest Ebola outbreak in history with more than 2200 lives lost and 3400 confirmed infections since the outbreak declared on 1 August 2018.
We came across MERS, SARS, Nipah, Marburg, yellow fever, Zika virus, dengue fever, Avian influenza, Swine flu, and many more in the last 20 years.
However, while we turn back the history pages, there were many viral outbreaks. In 1347, black death claimed 200 million human lives, in 1796, Smallpox took 300 million lives, influenza pandemic in 1918 lost 50 to 100 million lives, HIV an ongoing viral infection with 32 million deaths so far.
Nevertheless, the disturbing fact is that since 1980 alone the number of outbreaks per year has more than tripled.
Where do all these viruses come from?
Unfortunately, we do not have a precise answer as viruses leave no fossils like dinosaurs or any other organisms, at least in the conventional sense.
For that reason, the study of virus evolution is challenging. All the viruses are obligate parasites and they work by hijacking the biochemical machinery of its host leaving the molecular fossils (fragments of genes on the host genome). To analyze the imprints left by the virus, one need to untangle all the host genome. For further difficulty viruses don?t just infect humans, they infect all the organisms including bacteria, animals, plants, etc.
Regardless, there are three main hypotheses on the origin of the virus.
Hypotheses on the origin of the virus
- Progressive hypothesis ? According to this hypothesis, the virus originated through a progressive process. Pieces of genetic material capable of moving within a genome gained the ability to exit one cell and enter another. Eg., a retrovirus.
? ? 2. Regressive hypothesis ? According to this hypothesis, viruses were once free-living organisms and had a? symbiotic relationship with other organisms and over time, this relationship became more parasitic and viruses adopted a parasitic approach to replication. Eg., smallpox virus, mimivirus.
? ? 3. Virus first model ? viruses predate or coevolved with their current cellular hosts. The above two hypotheses assume cells exist before the virus, what if viruses exist first? Viruses existed in a precellular world as self-replicating units.
For the time being, these are? only hypotheses and are debatable.
Momentarily, we can keep the evolutionary origin of the virus apart and look at how new viral diseases are emerging as endemics.
There are over 200 ICTV (International Committee on Taxonomy of Viruses) recognized virus species that are known to infect humans.
Not all newly identified viruses are new in the sense that they have recently started infecting humans. Coronavirus has been circulating for almost 40 years. SARS-CoV-2 causing the COVID-19 is the seventh known coronavirus to infect people, after 229E, NL63, OC43, HKU1, MERS-CoV, and the original SARS-CoV.
The biological perspective of virus emergence
Let?s track down the biological context in the emergence of viruses and viral disease outbreaks.
The process of virus emergence can be divided into 4 stages.
Stage 1: Exposure
- Source of exposure
- Acquisition of a virus from the source
- Rate of exposure
Source of exposure
The human population is exposed to a potential source of the virus. The potential virus source is most likely zoonotic, such as other mammals, with rodents as the most common, followed by primates, carnivores, and bats. A minority of the zoonotic viruses are also known to find in birds.
Therefore, some of the viruses are believed to have originated in other mammal or bird species, and could be exposed to humans:
HIV-1 (derived from a simian immunodeficiency virus found in chimpanzees); severe acute respiratory syndrome virus (SARS; horseshoe bats); hepatitis B, human T-lymphotropic virus (HTLV)-1 and -2, dengue and yellow fever (all primates); measles, mumps and smallpox (all livestock); and influenza A (wildfowl).
The acquisition of the virus from the potential source to the human body might be through contact with blood, saliva, feces, contamination of food and water, or via arthropod vectors, etc.
According to the World health organization (WHO), Ebola virus was introduced into the human population through close contact with the blood, secretions, organs or other bodily fluids of infected animals (animal sources of viruses) such as fruit bats, chimpanzees, gorillas, monkeys, forest antelope or porcupines found ill or dead or in the rainforest.
Dengue is a mosquito-borne viral disease caused by the dengue virus (DENV) of the Flaviviridae family. It is transmitted by female mosquitoes mainly of the species Aedes aegypti and, to a lesser extent, Ae. albopictus.
The Nipah outbreaks in Bangladesh and India could be due to the consumption of fruits or fruit products (such as raw date palm juice) contaminated with urine or saliva from infected fruit bats.
Rate of exposure
The rate of exposure is determined by the combination of many factors including the distribution and ecology of the non-human host (potential source) and human activities.
Host distribution, host ecologies, host behavior/contact ratio, virus transmission route all play a major role in the process of exposure.
Stage 2: Infection
This stage represents a subset of viruses capable of infecting humans ie, they must overcome the species barrier to establish infection.
For viruses, one of the key steps in the emergence process is the jump between one host species and humans.
For a successful jump into a new species,
- Access ? Viruses should have access to enter the new host to cause infection by specifically binding to the receptors located on the target tissue before the host immune cells kick it off.
- The ability of the virus – Once inside, it must be able to replicate itself enough, exit the host and to infect and transmit itself to other members of the same species. (Most viruses jump will result in the dead-end host)
Various factors affect the virus’s ability to jump including taxonomical relatedness to the host, geographical overlap, and host range.
The host range is a highly variable trait among viruses. For example, rabies ? infect a wide range of mammals while Mumps, specialize on a single host (humans). Moreover, the host range is phylogenetically labile, with even closely related species having very different host ranges. The physiology of the exposed human population also plays a crucial role.
Stage 3: Transmission
Stage 3 represents the subset of viruses that can not only infect humans but can also be transmitted from one human to another by whatever route.
Unless the virus is not able to transmit from one person to another, it?s a dead-end host for the virus.
For example, H5N1 is a type of influenza A virus that causes a highly infectious, severe respiratory disease in birds called avian influenza (or “bird flu”). According to WHO, human cases of H5N1 avian influenza have been associated with close contact with infected live or dead birds, or H5N1-contaminated environments. The virus does not spread from person to person. Therefore, we can say this virus cannot pass to stage 3 of the pyramid.
The transmission potential of the virus in the human to human transmission mainly reflects the virus-host interaction, especially whether it is possible for the virus to access tissues from which it can exit the host such as the upper respiratory tract, lower gut, urogenital tract, skin or blood.
Tissue tropism (tissue tropism is the cells and tissues of a host that support the growth of a virus) play a significant role here. Some viruses have a broad tissue tropism and can infect many types of cells and tissues while other viruses may infect primarily a single tissue.
The seasonal influenza A viruses have a greater transmission rate compared to the avian influenza virus. One reason for this could be due to the superior ability of the seasonal influenza viruses to colonize the upper respiratory tract. Particles in the upper respiratory tract are moved quickly towards the pharynx. This environment favors the virus by the generation of virus-containing droplets. Moreover, tissue inflammation at this site could also stimulate sneezing, enhancing further transmission.
Human studies and animal models (mice and non-human primates) have detected extensive tissue tropism in zika virus, detecting the virus in multiple body fluids.
Stage 4: Epidemic spread
This stage represents a subset of viruses that are capable of sufficiently transmitting between humans can cause major outbreaks and/or become endemic in the human population without the requirements of a non-human reservoir.
The error rate in the viral replication is higher compared to other organisms and the virus lacks the proofreading enzymes to check these errors resulting in higher mutation rates. Mutation in viral replication (Nucleotide substitution, recombination/reassortment selection, etc.) might be damaging to the virus, but some of those mutations will enable the virus to infect a new host more effectively and thereby, causing an endemic or pandemic.
Reproductive ratio (R0), is a mathematical modeler of disease dynamics which measures a virus’s ability to cause an outbreak. R0 is the number of secondary cases in a population caused by a single case, assuming that all other members are susceptible. When R0 is >1, the virus will multiply within a population and cause an outbreak.
There could be several factors including environmental or ecological changes affecting the R0 of wildlife viruses to rise above 1 in human populations.R0 could also be proportional to host density, so that there is a critical threshold of human population density, below which a virus will fade to extinction.
Increasing densities of human populations in urban centers and the increasing rates of movement of people between cities and countries will increase R0 and the risk for new epidemic zoonoses.
Factors affecting the virus emergence process
Some factors drive the process of virus emergence. The most important drivers of virus emergence process are environmental and biological factors, urbanization and land use, global travel, intensification of livestock production, population growth.
Abundant diversity of viruses exists in the world, each with its characteristics and epidemiology. The driving factors could favor one virus over the other in the biological emergence process, which response by invading its new habitat and causing endemics.
And this could result in the advent of new viruses more often.