#### xaktly | Virology

Viruses – introduction

The virology pages are organized like this:

### What are viruses?

First, let's think about why we need to understand viruses. Here are some good reasons:

#### 1. Viruses are everywhere

Viruses are ubiquitous on Earth. No single organism is unaffected by viruses, whether in a benign way or adversely. Nothing escapes. Humans regularly eat and breathe billions of viruses every day.

The waters of Earth contain about 1030 viruses. If each virus, on average, has a mass of about 1 femtogram (fg) (1 fg = 1 × 10-15 g), then the mass of all those viruses is about

$$(1 \times 10^{30})(1 \times 10^{-15}) = 1 \times 10^{15} \, g$$

That's about 300 times the mass of the estimated number of humpback whales on Earth in 2021 (125,000 whales at an average of 30,0000 Kg each). That's a lot of mass for something you can't see.

#### 2. Viruses can cause disease

While most viruses cause no harm, some cause significant disease. Think about measles, smallpox, polio, influenza and other illnesses that once did or still do claim many human lives every year. Humans carry many viruses in all cell types, many of which are even beneficial, and our genomes are packed with old viral DNA that has been incorporated and passed down through our evolution. Viruses affect respiratory, digestive, blood and other systems of all animals. They affect plants, bacteria, fungi, archea – all organisms.

All humans, by the age of 10 or so, have been exposed to and carry:

• Herpes simplex viruses (HSV1, HSV2)
• Human herpes viruses (HHV-6,7,8)
• Varicella zoster (chickenpox) virus (VZV)
• Human cytomegalovirus (HCMV)
• Epstein-barr virus (EBV)

If you are reading this, then you're carrying these viruses around in your cells. It's inescapable.

Like all living things on Earth, the genomes of viruses change over time because of small, random copying errors (evolution doesn't have a purpose). Because the generation time of a virus can be very short, any virus has millions of opportunities to gain some new function, such as the ability to dodge an antiviral drug, over the course of a human lifetime.

As an example, there are estimated to be about 1016 different HIV (the virus that causes AIDS) genomes currently cirulating on Earth. That practically ensures that there is one mutation capable of getting around any of the dozen or so antiviral drugs we currently have to keep HIV infections in check. Our only hope of keeping infected people well is to keep the virus population in each person low enough that those mutants can't get a foot-hold.

#### 4. Viruses can jump between hosts

A zoonotic transfer is a transfer of a virus from a non-human to a human host. There is evidence, for example, that the Severe Acute Respiratory Virus (SARS) outbreak of 2003 originated in species of bat in China, jumped to Civets and then to humans. These transfers happen when a random mutation renders a virus (again, by accident) fit to infect a subset of cells of a different species. Some viruses have no apparent effect on hosts like bats, so they can persist in those animals, mutating along the way until one of those mutations allows for transfer. We need to understand these processes so that we can better respond to or even anticipate future lethal virus outbreaks, like that which caused the SARS-CoV-2 pandemic of 2020-21.

Here is a fairly concise definition of what a virus is. We'll dig into it below.

#### Definition of a virus

Viruses are obligate intracellular parasites which contain an RNA or DNA genome surrounded by one or more protein coats, and possibly a membrane, usually derived from its host cell. Virus and host usually share a long co-evolution.

Let's pick that definition apart:

An obligate intracellular parasite is one that must enter a cell in order to be reproduced. Viruses, in fact, have no means to reproduce themselves. They rely wholely or almost so on the DNA or RNA copying machinery of their host cells to reproduce their genomes. Viruses have to be inside a host cell in order to be reproduced, and therefore to infect more cells.

All viruses (indeed, all living things on Earth) contain a genome, a set of instructions encoded in an RNA or DNA polymer.

Viruses are often little more than a protein shell that surrounds this genome, sometimes in one layer, sometimes in two. Some viruses enclose one or more enzymes that their host cells don't contain and which allow them to replicate their genomes despite the deficiency.

Finally, many viruses obtain a membrane coating as they exit their host cells. It is derived from the phospholipid bilayer membrane of the cell.

Viruses come in many forms, but they all have far more in common than differences. Here are some electron micrographs to set the stage. Each is far, far smaller in size than a typical cell.

The Ebola virus.

The Corona virus.

The Lambda phage (a phage is a virus that infects bacteria).

### Are viruses alive?

I'll give my answer to this question first, then try to explain it: Viruses are not alive. It hardly really matters, however, because, as we've already said above, viruses infect / affect every living cell, so they're an unavoidable part of life.

Here are seven characteristics of all living things with a brief discussion of how viruses fit in (or don't): Living things

1. consist of one or more cells. Virus particles are made of simple arrangements of proteins, some surrounded with membrane material borrowed from the host cell, but they are not cells. They do not contain most of the things we'd expect to find in cells.

2. are homeostatic. Homeostasis is the ability of an organism to regulate its own environment, such as controlling its own temperature, internal pressure or pH. Viruses can do none of these.

3. make energy. Viruses do not have anything like cellular metabolism. They don't contain mitochondria or have anything like a Kreb's cycle.
1. grow. Viruses are assembled inside their host cells, and they don't add any mass afterward. They do not grow.

2. adapt by evolution. This is a trickier one. Viruses certainly mutate, but not without the genome replication machinery of the host cell. They do not mutate outside of the host cell. Cells of living organisms reproduce their own genomes constantly, and errors that could cause mutations constantly accrue.

3. respond to stimulus. While cells can respond to stimulus of all kinds – think gravity, sunlight, temperature, and so on – viruses do not. And finally,

4. reproduce. While cells reproduce by division and organisms reproduce sexually or otherwise, viruses are entirely dependent on co-opting host-cell machinery in order to be replicated.

Science writer Alan Dove takes a different tack, defining a living thing as something with the ability to be infected by viruses.

### An ancient connection

Humans and viruses have shared an intertwined path throughout their mutual evolution. Some viruses, retroviruses, have the ability to insert parts of their genomes into the DNA of the host cell. Over the history of human evolution, many fragments of viral DNA have been inserted into our genome by retroviruses. Consider the pie chart of the human genome:

Let's discuss a few of these categories:

• Protein-coding genes: It is remarkable that only about 2% of the 3.2 × 109 base pairs of the human genome is dedicated to protein-coding genes – the stuff we're made of. That leaves us to figure out the purpose of a lot of extra DNA we carry around.
• SINEs and LINEs: These are short and long interspersed nuclear elements, respectively. Most are likely insertions made by viruses into our ancestral DNA. They have been passed down through the evolution of humans, and now play various roles in turning genes on and off, forming chromatin – the thickly-coiled form of DNA that we can see under a microscope when we view chromasomes, and a few other as yet not fully-understood processes.

• LTRs are long terminal repeats. They are repeating segments of DNA, often several hundred bases long, that flank both ends of a retro-transposon, the DNA of a retrovirus that has inserted its genome before. There are thousands of these in the human genome; they constitute about 8% of it.

• Introns are non-coding stretches of DNA that interrupt coding genes. In order for the gene to be transcribed into an mRNA, the intron must be skipped, the intron portion must be removed from the mRNA, or the resulting protein must be modified after translation. The origin of introns is still unclear, but they do seem to play a role in regulation of gene expression.

### How big (small) are viruses?

Because viruses can enter cells, they have to be smaller than cells. Their capsids are made of medium-sized proteins, so one way to look at them is as large macromolecules. The figure shows that their size is just between the smallest cells (like red blood cells or bacteria) and large protein assemblies like the ribosome.

Most viruses are too small to view using a light microsope, so we have to use an electron microscope or a diffraction (electron or x-ray) technique.