Here’s an age-old question: Where do infectious diseases come from?  Until about 130 years ago, we thought they only  came from microscopic organisms, like bacteria.  So, when a disease started rotting  tobacco plants across Europe,   scientists and farmers went  looking for the culprit.  And they found something… a bit unexpected.

Russian botanist Dmitri Ivanovsky took some   sap from an infected plant and passed it  through a filter to strain out the bacteria.  Except, even without bacteria, the sap from  the infected plants still spread the disease.  Turns out, it was spreading through what  was then perceived to be a “contagious   living fluid,” not a bacterium at all. Dutch botanist Martinus Beijerinck dubbed   it a “virus,” from the Latin word for poison.

In fact, while they’re not quite alive,   viruses have been growing and evolving  alongside life for billions of years. Hi, I’m Dr. Sammy, your friendly neighborhood  entomologist, and this is Crash Course Biology.  I’m sorry guys, someone sneezed on the theme music  yesterday and I think it’s not feeling well…Oh,   wait, you’re gonna still do it?

Oh, sweet! Okay… [THEME MUSIC] While most scientists wouldn’t  classify viruses as alive,   they do have a lot in common with living things.  Like living things, they come  in diverse shapes and sizes.  There are viruses that look like uncooked  spaghetti, spiky dog toys, or spacecrafts.  But, for the most part, they’re smaller and much  less complicated than even the simplest bacteria.  For example, the influenza virus that  causes the seasonal flu can be 100 to   1,000 times smaller than a human cell. Even the most jumbo-sized viruses are   minuscule—barely visible with a light microscope.

And they’re simpler, too.  The bacterium E. coli has more than 4000 genes. The influenza virus only has eight!  And, yeah: viruses have genes,  just like us living things.  But they exist as an infectious bunch  of nucleic acids — with single or   double strands of DNA or RNA — wrapped in a  protein jacket called a capsid, and sometimes   an outer membrane called a viral envelope. “Capsid'' comes from the Latin word for “box.”  So, you can think of a virus as “genes in a box.” Viruses also evolve over time – which is why your   body can develop an immune response to  a virus, but then get infected by a new   variation that evades those defenses. And if you’re wondering how all this is   possible for something that isn’t  “alive,” well, so are scientists.  We don’t really know yet, but  we have some pretty good ideas.

One, is that viruses arose from  genetic material gone rogue,   which gained the ability to escape from cells  and move between them, hopping from cell to cell.  Genetic material has to leave the nucleus  to inform the protein-making process,   so it’s not that huge a leap that  it could leave the cell altogether.  Another is that viruses evolved from living  organisms that went minimalist — reducing   and simplifying themselves and losing  genetic information along the way, until   they were more life-adjacent than actual life. It’s also possible that viruses existed before   cells, as very simple RNA molecules  that could replicate on their own.  And only evolved to infect cells after  the first living things showed up.  If you want a refresher on the currently accepted   criteria for what counts as “alive,”  you can find that back in episode 1.  But it’s important to remember  that the concepts of “living”   and “nonliving” are just that, concepts. We try to fit the complicated world into   neat little bins because it serves  to make complexity easier to manage.  But the natural world isn’t  always so easily defined.

The exact evolutionary relationship  between life and viruses isn’t yet clear.  But the important thing is, viruses  can’t reproduce, grow, process energy,   or do anything on their own that resembles living. It’s only when they bump into, and infect,   the right cell, called a host,  that viruses can function.  Each different type of virus can  only infect a certain range of hosts.  Like, take bacteriophages, for example, a  type of virus that can infect only bacteria.  Or the virus that causes measles,  which infects only primates.  Of course, not all viruses are  limited to closely-related species.  We know that SARS-CoV-2, the virus causing  COVID-19, has invaded cells in humans,   hamsters, white-tailed deer, and more. When viruses can infect people and other   animals, we consider them zoonotic diseases.

When a virus bumps into a cell it’s capable   of infecting, it can enter and take  over, taking control of the molecular   machinery of life to make copies of the  virus so it can spread to more cells.  This is what we mean by “viral”: One  cell gets taken over, then another.  If a bunch of cells end up  controlled by the virus,   it can spread faster than a video of a  cat in a t-shirt playing the keyboard.  And while there’s more than one way a  virus can hijack a molecular copy-machine,   many of the viruses you may have heard of  before—like polio, measles, mumps, and the   common cold—take the same basic approach. Let’s head over to the Thought Bubble… Meet the typical RNA virus: floating  around in its spiked envelope.  On its own, it can’t do  much other than drift about.  But if it comes across a compatible  host cell, it’s suddenly very active.  That spike latches onto the cell’s receptor,  bringing the envelope close to the cell   membrane so the two can fuse together. The virus then barges into the cell,   making itself at home.

It sheds its capsid — the   inner jacket — exposing a single strand of  RNA, with clear instructions: replicate.  A special viral enzyme commands the cell’s energy  and machinery to make copies of the RNA strand.  Some of those copies then act as messenger RNA,  and the cell translates them into viral proteins.  Those proteins then wrap  around the other RNA copies,   becoming capsids for whole new viral particles.  Before those new viruses split off  from the cell and make their exit,   they shroud themselves in the cell membrane,  fashioning it into their own spiked envelopes.  And with that, they drift away—brand-new  viruses, waiting to bump into other host cells.  Thanks, Thought Bubble! This cellular takeover   is how most RNA viruses replicate and spread. And by the time that replication is finished,   the virus has often interrupted normal cellular  functions, harming, or even killing the host cell. …sooooo yeah I’m just…I’m just gonna  say it, viruses are kinda rude right?

And while all of that is normal for a typical RNA  virus, there’s another type of virus, called a   retrovirus, that takes the process even further. After the retrovirus enters the host, its RNA   transforms into DNA, a process that’s helped along  by a special enzyme called reverse transcriptase.  That viral DNA then integrates into the  host cell’s DNA — becoming one with it.  In fact, one-tenth of the human genome  carries fragments of viral DNA from   ancient infections embedded in our ancestors’  reproductive cells and passed down to us.  They don’t hurt us like active viruses, in  fact, some have even evolved into helpful genes.  But HIV, the virus that causes AIDS,  is a serious example of a retrovirus.  It spreads from person to person through direct  contact with certain infected body fluids:   like blood, semen, vaginal fluids, and breastmilk.  It infects the host’s T cells,  a key part of the immune system.  After entering the host cell’s DNA, the HIV DNA  can sit silently for sometimes more than ten years   before transcribing back into RNA and making  new viral particles that infect other cells.  HIV particles kill off each host cell as they  spread, and since those cells are important in   fighting off infections, they eventually  weaken the whole body’s immune system. The good news is, we’ve come a long way  since Beijerinck first identified his   “contagious living fluid” as a virus.

These days, we can fight back against   viral invaders with two pretty great  defenders: vaccines and antivirals.  Vaccines are central to our  resistance against viral invaders.  If a virus is an invader, and our immune systems  are an army, then a vaccine is boot camp: A form   of training that lets cells practice fighting  the virus, without the threat of a real invasion.  You see, viruses can travel virtually  undetected, and until our cells meet one,   they don’t know how to recognize them. Which puts our cells at a disadvantage.  So, vaccines let the body’s immune system  learn first, introducing it to bits of the   virus—like just its protein jacket—or a  very weak or “dead” version of the virus.  That version isn’t able to spread or replicate  — but it makes for great boxing practice.  More recently, vaccines have been successful  at battling COVID-19 by using messenger RNA.  An mRNA vaccine carries a slice of instructions  for making a virus’s spiked protein.  Remember, this is like the key that  the virus uses to unlock the cell.  When the vaccine is injected, our cells  follow the instructions and make the spiked   protein — which is harmless by itself,  but great at helping our immune system   recognize and learn to fight the actual virus. And, while there is no vaccine to prevent HIV yet,   we do have another defender ready to  step up to help combat this deadly virus.  Let’s learn a little more in the Theater of Life… In 1990, HIV infections were  on the rise in South Africa.  And epidemiologist Dr.

Quarraisha Abdool Karim  wanted to understand how they were spreading.  So, she visited a number of  rural South African communities.  There, she learned that women didn’t have  a method of protection from the virus that   they alone could control, regardless  of their sexual partners’ behavior.  Dr. Abdool Karim knew of gels called  microbicides that women could apply   before and after sex to protect  themselves against other infections.  So, what if a gel could do  the same thing…but with HIV?  For nearly two decades, she pursued this  idea, testing two different microbicides   in search of a preventive medicine. Neither of those first drugs stopped HIV.  But in 2010, she and her team finished testing  a third microbicide, tenofovir, in a trial   with South African women that lasted three years.

When used regularly by women before and after sex,   the tenofovir gel cut rates  of HIV infection in half.  That gave them a way of protecting  themselves that they could control.  By going to communities first, Dr. Abdool  Karim leveraged science in a powerful way:   first figuring out where help was needed,  then finding the right tool for the job.  Medicines, like the one Dr. Abdool  Karim developed, are called antivirals.  They help battle viral infections once they’ve  begun, but instead of killing the virus,   they capitalize on its number-one weakness.

Without a host cell, a virus can’t replicate.  So, some antivirals essentially barricade  cells to keep the virus from getting in.  Other antivirals work within the cell,  throwing a wrench into the machinery — like,   interrupting important enzymes,  so viral copies never make it out.  Or amping up the body’s whole immune  system—releasing proteins that turn the   “attack mode” dial on high, and putting  other cells on guard for invaders.  Together, vaccines and antivirals represent some  big steps in the way science combats viruses. They may just be genes in a box, but, it’s  clear that viruses are entwined with life.  They’re old, ancient things — and yet, new ones  are emerging all the time, posing new and unique   threats, as we’ve seen with COVID-19. But the more we learn about them,   the more fine-tuned our defenses get.

And the more we can protect   ourselves and each other. Next time, we’re going to look at the ways   biologists, and other scientists, use computers  to better understand the world around us.  I’ll see ya then! Peace!

This series was produced in  collaboration with HHMI BioInteractive.  If you’re an educator, visit  BioInteractive.org/Crashcourse for   classroom resources and professional development  related to the topics covered in this course. Thanks for watching this episode of Crash  Course Biology which was filmed at our studio   in Indianapolis, Indiana, and was made  with the help of all these nice people.  If you want to help keep Crash  Course free for everyone,   forever, you can join our community on Patreon.