Target Health Blog

Quick Glimpse of Viral History

May 25, 2020

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History of Medicine
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Overview of the main types of viral infection and the most notable species involved
Graphic credit: by Mikael Haggstrom.When using this image in external works, it may be cited as:Haggstrom, Mikael (2014). “Medical gallery of Mikael Haggstrom 2014“. WikiJournal of Medicine 1 (2). DOI:10.15347/wjm/2014.008. ISSN 2002-4436. Public Domain.or by Mikael Haggstrom, used with permission. - All used images are in public domain. Wikipedia Commons; NIAID.gov (Anthony Fauci MD)

Eukaryotes include such microorganisms as fungi, protozoa, and simple algae. Viruses are considered neither prokaryotes nor eukaryotes because they lack the characteristics of living things, except the ability to replicate (which they accomplish only in living cells). Viruses are much, much smaller than prokaryotes. Prokaryotic and Eukaryotic cells are both alive, while viruses are not. Viruses have very few organelles, similar to the prokaryotic cells. They contain a plasma membrane, cell wall, RNA or DNA, and a protein capsule. Prokaryotic cells lack internal membrane-bound structures and are unicellular organisms. One example of a prokaryote is bacteria. Prokaryotic cells are about one-tenth the size of a eukaryotic cell. A prokaryote's DNA is double-stranded, and it prokaryotic cell is also experiences chemiosmosis. Eukaryotic cells are multicellular organisms that have membrane-bound organelles, such as animal cells. Some eukaryotic cells, however, are unicellular organisms such as amoebas. Eukaryotic cells are present in all living things except bacteria.

Viruses are disease-causing, nonliving particles composed of an inner core of nucleic acids surrounded by a capsid. They have a plasma membrane, cell wall, and a proteins capsule. They also contain either RNA or DNA, which can be either single stranded or double stranded. Viruses cannot make their own energy or reproduce, so they attack other host cells and use its energy to replicate themselves. Compared to a eukaryotic cell, a virus is tiny. The origins of viruses in the evolutionary history of life are unclear: some may have evolved from plasmids, which are pieces of DNA that can move between cells, while others may have evolved from bacteria. The variety of host cells that a virus can infect is called its “host range“.

Strictly speaking, viruses cannot die, for the simple reason that they aren't alive in the first place. Although they contain genetic instructions in the form of DNA (or the related molecule, RNA), viruses can't thrive independently. Instead, they must invade a host organism and hijack its genetic instructions. Viruses are important microbial predators that influence global biogeochemical cycles and Eukaryotes include such microorganisms as fungi, protozoa, and simple algae. Viruses are considered neither prokaryotes nor eukaryotes because they lack the characteristics of living things, except the ability to replicate (which they accomplish only in living cells). Viruses are much, much smaller than prokaryotes. Prokaryotic and Eukaryotic cells are both alive, while viruses are not. Viruses have very few organelles, similar to the prokaryotic cells. They contain a plasma membrane, cell wall, RNA or DNA, and a protein capsule. Prokaryotic cells lack internal membrane-bound structures and are unicellular organisms. One example of a prokaryote is bacteria. Prokaryotic cells are about one-tenth the size of a eukaryotic cell. A prokaryote's DNA is double-stranded, and its prokaryotic cell is also experiencing chemiosmosis. Eukaryotic cells are multicellular organisms that have membrane-bound organelles, such as animal cells. Some eukaryotic cells, however, are unicellular organisms such as amoebas. Eukaryotic cells are present in all living things except bacteria.

Viruses are disease-causing, nonliving particles composed of an inner core of nucleic acids surrounded by a capsid. They have a plasma membrane, cell wall, and a proteins capsule. They also contain either RNA or DNA, which can be either single stranded or double stranded. Viruses cannot make their own energy or reproduce, so they attack other host cells and use its energy to replicate themselves. Compared to a eukaryotic cell, a virus is tiny. The origins of viruses in the evolutionary history of life are unclear: some may have evolved from plasmids, which are pieces of DNA that can move between cells, while others may have evolved from bacteria. The variety of host cells that a virus can infect is called its “host range“.

Strictly speaking, viruses cannot die, for the simple reason that they are not alive in the first place. Although they contain genetic instructions in the form of DNA (or the related molecule, RNA), viruses cannot thrive independently. Instead, they must invade a host organism and hijack its genetic instructions. Viruses are important microbial predators that influence global biogeochemical cycles and drive microbial evolution, although their impact is often under appreciated. Viruses reproduce after attaching and transferring their genetic material into a host cell.

Prokaryotic vs. Eukaryotic

A prokaryotic cell is much smaller than a eukaryotic cell and has many less organelles. A eukaryotic cell has distinct membrane-bound organelles such as mitochondria, ribosomes, golgi complex, endoplasmic reticulum, nucleus, chloroplasts, cell wall, plasma membrane, cytoplasm, vacuoles, centrioles, cilia, flagella, and lysosomes. A prokaryotic cell simply has ribosomes, plasma membrane, and a cell wall. Both animal cells and plant cells are eukaryotes, but they differ in structure and organelles. Animal cells have centrioles and mostly small lysosomes, while plant cells do not have centrioles and have larger lysosomes. Plant cells are characterized by a cell wall, chloroplasts, and one large vacuole.

Evolutionary History of Viruses

The evolutionary history of viruses represents a fascinating, albeit murky, topic for virologists and cell biologists. Because of the great diversity among viruses, biologists have struggled with how to classify these entities and how to relate them to the conventional tree of life. They may represent genetic elements that gained the ability to move between cells. They may represent previously free-living organisms that became parasites. They may be the precursors of life as we know it. To consider this question, we need to have a good understanding of what we mean by “life.“ Although specific definitions may vary, biologists generally agree that all living organisms exhibit several key properties: They can grow, reproduce, maintain an internal homeostasis, respond to stimuli, and carry out various metabolic processes. In addition, populations of living organisms evolve over time. Do viruses conform to these criteria? Yes and no. We probably all realize that viruses reproduce in some way. We can become infected with a small number of virus particles by inhaling particles expelled when another person coughs for example, and then become sick several days later as the viruses replicate within our bodies. Likewise, we probably all realize that viruses evolve over time. We need to get a flu vaccine every year primarily because the influenza virus changes, or evolves, from one year to the next.

Viruses do not, however, carry out metabolic processes. Most notably, viruses differ from living organisms in that they cannot generate ATP. Viruses also do not possess the necessary machinery for translation, as mentioned above. They do not possess ribosomes and cannot independently form proteins from molecules of messenger RNA. Because of these limitations, viruses can replicate only within a living host cell. Therefore, viruses are obligate intracellular parasites. According to a stringent definition of life, they are nonliving. Not everyone, though, necessarily agrees with this conclusion. Perhaps viruses represent a different type of organism on the tree of life - the capsid-encoding organisms, or CEOs.

Where Did Viruses Come From?

There is much debate among virologists about this question. Three main hypotheses have been articulated: 1) The progressive, or escape, hypothesis states that viruses arose from genetic elements that gained the ability to move between cells; 2) the regressive, or reduction, hypothesis asserts that viruses are remnants of cellular organisms; and 3) the virus-first hypothesis states that viruses predate or coevolved with their current cellular hosts.

The Progressive Hypothesis

According to this hypothesis, viruses originated through a progressive process. Mobile genetic elements, pieces of genetic material capable of moving within a genome, gained the ability to exit one cell and enter another. To conceptualize this transformation, we can use the replication of retroviruses, the family of viruses to which HIV belongs. Retroviruses have a single-stranded RNA genome. When the virus enters a host cell, a viral enzyme, reverse transcriptase, converts that single-stranded RNA into double-stranded DNA. This viral DNA then migrates to the nucleus of the host cell. Another viral enzyme, integrase, inserts the newly formed viral DNA into the host cell's genome. Viral genes can then be transcribed and translated. The host cell's RNA polymerase can produce new copies of the virus's single-stranded RNA genome. Progeny viruses assemble and exit the cell to begin the process again.

This process very closely mirrors the movement of an important, though somewhat unusual, component of most eukaryotic genomes: retrotransposons. These mobile genetic elements make up an astonishing 42% of the human genome and can move within the genome via an RNA intermediate. Like retroviruses, certain classes of retrotransposons, the viral-like retrotransposons, encode a reverse transcriptase and, often, an integrase. With these enzymes, these elements can be transcribed into RNA, reverse-transcribed into DNA, and then integrated into a new location within the genome. It can be hypothesized that the acquisition of a few structural proteins could allow the element to exit a cell and enter a new cell, thereby becoming an infectious agent. Indeed, the genetic structures of retroviruses and viral-like retrotransposons show remarkable similarities.

The Regressive Hypothesis

In contrast to the progressive process, viruses may have originated via a regressive, or reductive, process. Microbiologists generally agree that certain bacteria that are obligate intracellular parasites, like Chlamydia and Rickettsia species, evolved from free-living ancestors. Genomic studies indicate that the mitochondria of eukaryotic cells and Rickettsia prowazekii may share a common, free-living ancestor. It follows, then, that existing viruses may have evolved from more complex, possibly free-living organisms that lost genetic information over time, as they adopted a parasitic approach to replication.

Viruses of one particular group, the nucleocytoplasmic large DNA viruses (NCLDVs), can illustrate this hypothesis. These viruses, which include smallpox virus and the recently discovered giant of all viruses, Mimivirus, are much bigger than most viruses. A typical brick-shaped poxvirus, for instance, may be 200 nm wide and 300 nm long. About twice that size, Mimivirus exhibits a total diameter of roughly 750 nm. Conversely, spherically shaped influenza virus particles may be only 80 nm in diameter, and poliovirus particles have a diameter of only 30 nm, roughly 10,000 times smaller than a grain of salt. The NCLDVs also possess large genomes. Again, poxvirus genomes often approach 200,000 base pairs, and Mimivirus has a genome of 1.2 million base pairs; while poliovirus has a genome of only 7,500 nucleotides total. In addition to their large size, the NCLDVs exhibit greater complexity than other viruses have and depend less on their host for replication than do other viruses. Poxvirus particles, for instance, include a large number of viral enzymes and related factors that allow the virus to produce functional messenger RNA within the host cell cytoplasm.

Because of the size and complexity of NCLDVs, some virologists have hypothesized that these viruses may be descendants of more complex ancestors. According to proponents of this hypothesis, autonomous organisms initially developed a symbiotic relationship. Over time, the relationship turned parasitic, as one organism became more and more dependent on the other. As the once free-living parasite became more dependent on the host, it lost previously essential genes. Eventually it was unable to replicate independently, becoming an obligate intracellular parasite, a virus. Analysis of the giant Mimivirus may support this hypothesis. This virus contains a relatively large repertoire of putative genes associated with translation -- genes that may be remnants of a previously complete translation system. Interestingly, Mimivirus does not differ appreciably from parasitic bacteria, such as Rickettsia prowazekii

The Virus-First Hypothesis

The progressive and regressive hypotheses both assume that cells existed before viruses. What if viruses existed first? Recently, several investigators proposed that viruses may have been the first replicating entities. It has been postulated that viruses existed in a precellular world as self-replicating units. Over time these units, they argue, became more organized and more complex. Eventually, enzymes for the synthesis of membranes and cell walls evolved, resulting in the formation of cells. Viruses, then, may have existed before bacteria, archaea, or eukaryotes. Most biologists now agree that the very first replicating molecules consisted of RNA, not DNA. We also know that some RNA molecules, ribozymes, exhibit enzymatic properties; they can catalyze chemical reactions. Perhaps, simple replicating RNA molecules, existing before the first cell formed, developed the ability to infect the first cells. Could today's single-stranded RNA viruses be descendants of these precellular RNA molecules?

No Single Hypothesis May Be Correct

Where viruses came from is not a simple question to answer. One can argue quite convincingly that certain viruses, such as the retroviruses, arose through a progressive process. Mobile genetic elements gained the ability to travel between cells, becoming infectious agents. One can also argue that large DNA viruses arose through a regressive process whereby once-independent entities lost key genes over time and adopted a parasitic replication strategy. Finally, the idea that viruses gave rise to life as we know it presents very intriguing possibilities. Perhaps today's viruses arose multiple times, via multiple mechanisms. Perhaps all viruses arose via a mechanism yet to be uncovered. Today's basic research in fields like microbiology, genomics, and structural biology may provide us with answers to this basic question.

According to the NIH, explaining the origin of viruses remains an important challenge for evolutionary biology. Previous explanatory frameworks described viruses as founders of cellular life, as parasitic reductive products of ancient cellular organisms or as escapees of modern genomes. Each of these frameworks endow viruses with distinct molecular, cellular, dynamic and emergent properties that carry broad and important implications for many disciplines, including biology, ecology and epidemiology. In a recent genome-wide structural phylogenomic analysis, it was shown that large-to-medium-sized viruses coevolved with cellular ancestors and have chosen the evolutionary reductive route. Results suggest two important phases in the evolution of viruses: (1) origin from primordial cells and coexistence with cellular ancestors, and (2) prolonged pressure of genome reduction and relatively late adaptation to the parasitic lifestyle once virions and diversified cellular life took over the planet. Under this evolutionary model, new viral lineages can evolve from existing cellular parasites and enhance the diversity of the world's virosphere.

Contemplating the origins of life fascinates both scientists and the general public. Understanding the evolutionary history of viruses may shed some light on this interesting topic. To date, no clear explanation for the origin(s) of viruses exists. Viruses may have arisen from mobile genetic elements that gained the ability to move between cells. They may be descendants of previously free-living organisms that adapted a parasitic replication strategy. Perhaps viruses existed before, and led to the evolution of, cellular life. Continuing studies may provide us with clearer answers. Or future studies may reveal that the answer is even murkier than it now appears.

Sources: www. nature.com/scitable/viruses; Wikipedia; nih.gov

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