Posted on 04/13/2003 1:14:01 PM PDT by Lessismore
The Sars virus is frightening not only because it's deadly but also because so little is known about it. Our medicine-trained senior writer taps expert knowledge to demystify the bug
GETTING TO KNOW YOU
YOUR Malicious Menace, you viruses are weird. Are you animate or inanimate? You can be freeze-dried and stay as a crystalline powder, so you seem inanimate. But add some water and nutrients, you come alive again. How so?
Czar of Sars: Knave! People who have severe acute respiratory syndrome (Sars) will tell you my viruses are very much alive.
We're not like other life forms for we don't have cells. We're really chains of genetic material - RNA or DNA - tucked inside a protein coat.
One thing we can't do, however, is reproduce ourselves, so we're always after the cells in you unsuspecting weaklings. Hey, we're better guerillas than Saddam's Republican Guards!
Your Royal Pain, why do you coronaviruses have crowns?
Dispense with your salutations!
Our family of 13 species has the royally largest genomes among all RNA viruses, even though we have just single-strand RNAs. (Yes, there are viruses with double-strand RNAs, single-strand DNAs, or even double-strand DNAs like you humans.)
On our outer coat are distinctive, club-shaped protein spikes which give us a crown-like appearance under your electron microscopes.
They're not just for show: The spikes enable us to bind with specific receptors on your cells. Once bound, we enter your cells, entertain ourselves taking over the machinery inside to replicate our particles, then we exit.
Enter, Entertain, Exit - that's your motto? Why other jewels on your coat?
Our coats are made up of a few types of protein, like the individual threads in a coat. The spikes are docking proteins that extend away from our coats so we can better dock onto specific receptor sites on your cells. Just think of our spikes and your sites as pairs of a velcro system.
Only some animal species and only some types of tissues within those species can form the velcro system with us.
For example, the common cold rhinovirus binds only to the human upper respiratory tract while herpes goes for nerve cells.
So besides wreaking havoc on our lungs, what else can you do?
You don't know much about us, do you? That's because we refuse to grow in most cell cultures that humans use to study our kind.
You can put half your miserable common colds down to us - rhinoviruses do the rest. Sometimes, we get infants in their guts.
In fact, as Sars shows, we can reach the heart, liver, bone marrow, and even nerves.
Some of our victims have died from multiple organ failure, not just pneumonia.
PIG MIXERS, ROAD SHOW
IT LOOKS like with Sars, you've hit the big time. How did you become so deadly?
As an RNA virus (like HIV), we mutate easily and often because we don't have DNA-based genes, which correct mistakes that occur during reproduction.
Aside from our spikes (S), we also have M- and H-proteins on our coats. We like to keep swopping and changing our S, M and H proteins, like our influenza cousins, so our coats never look the same.
Again, this isn't cosmetic. We change our coats yearly so our offspring look different. Your cells can't learn to recognise them fast enough to send out the troops to kill them.
But we have much to learn from our flu cousins, who have 15 varieties of H and nine varieties of N (neuraminidase) proteins to choose from. Think about their possible permutations (15!9!) Alas, we have far fewer.
But this didn't get Sars on the road, I'm told. How did you do it? Your scientists call it the pig mixer. How attractive. We Sars viruses are not one of the two known human coronaviruses; we probably came from animals.
Here's how: Like Cousin Flu, we infect not only humans but also cattle, pigs, rodents, cats, dogs and birds (ducks and chickens).
Pigs get pig coronaviruses but they also get those that infect birds and rodents or humans.
Say a rodent coronavirus and a bird coronavirus both infect the same pig cell but they get confused. Instead of getting that pig cell to crank out their individual viruses, the pig cell churns out mixed versions.
Think of the different sets of genes all mixed together - several hundred varieties of these blends are possible.
With our new spikes, we can hook onto your upper respiratory tract cells and also the cells of other organs in your body.
We first did it in Guangdong, China, last November. We had new hybrids which jumped into humans living close to the pigs and chickens they reared, and where rats and roaches ran free.
The Sars Road Show has been around the block a few times since then?
Yes, a Guangdong doctor took us to Hongkong, and from there, the rest of the world. We got to Singapore through three women.
Where specifically inside the hapless doctor did you hide?
We grew in the moist lining of his upper respiratory tract. A cough or sneeze propelled us out on a bit of moisture. But we were too large to get more than a metre away.
That's why we need to get up close and personal to a potential new host.
But most viruses do not survive outside the human body for long. So how did you manage to cross the globe in one month?
By jet, of course! Isn't that how everyone travels? Last Thursday, a 48-year-old male we had infected flew Lufthansa from Hongkong to Munich, Germany; Barcelona, Spain; Frankfurt, Germany; London, England; Munich again; Frankfurt again and then back to Hongkong before being warded there.
Whether he spread us to anyone else on these flights, we are not telling, but it helps that we can also spread by indirect contact.
If a droplet with us in it lands on an inanimate object, people can catch us simply by touching it. Some of our favourite things are door knobs and lift buttons.
You'd be amazed how far we can go.
So masks, gloves and frequent hand washing would do a good job of cutting your travel.
Yes, but we can also pass down your gut so if you don't wash your hands after using the toilet, we could be wallowing in tiny amounts of excrement on your fingers, which you could then spread around.
In fact, your people say this is how we could have swept like wildfire through the Amoy Gardens apartment block in Kowloon over the last weekend in March. We got 300 people who never came close to a Sars patient.
They say that cockroaches could have tracked us from sewage pipes into apartments. I'm not giving anything away but think about it: We'd be that much harder to contain.
A LITTLE HELP FROM FRIENDS
SURELY you are not claiming all the credit for the mayhem? Did you get some help from a paramyxovirus?
No, the paramyxovirus is just not in our class. But the metapneumoviruses, maybe. Hardy blokes who can survive on inert surfaces for six hours and on your hands for 30 minutes - longer than us, in fact.
Sure, they've never achieved our severity and our high attack rates in humans, but together we could do some real damage. But I'm not saying anything.
At least tell us what sex has to do with it?
All right. In China, they found chlamydia in the lungs of some of our victims. Now chlamydia is usually a sexually transmitted disease which can leave women infertile. Your people are saying we might have worked with an airborne form of that bug.
Naturally, people who already have chlamydia may be more vulnerable to us. Perhaps, they are the highly contagious 'super-spreaders' with very heavy viral loads?
I think you're more bluster than bite.
I admit, this year jet travel has made us look good.
But we still cause one mean illness, don't we? True, we have only killed 3 to 4 per cent of patients, but we're still perfecting our genetic arsenal, so watch out!
Okay, okay. Whatever the case, why are you so hard to knock out even now?
We're hard to kill because we reproduce inside living cells, so your drugs must be able to get into your cells but knock only us out.
Now, you have drugs which can do damage to our protein or nucleic acid synthesis, but they also kill your healthy cells. That's why we are so hard to deal with.
Some stupid scientist has developed a compound to block our RNA, in the way that zipping a bit of cloth into a zipper jams it. But is it safe to use in humans? You won't know till they do trials.
What are humans to do then?
Your best bet, if I may offer some advice, is still vaccination. But a vaccine ready for human use would take years to develop, by which time we would have new and improved spikes.
WHERE ART THOU?
SO VACCINES are a long way off and we've got to fight you with whatever we have. Right now, we know you've got another victim only when he comes down with fever, cough and chest pain from pneumonia. Is there no way to find out if you are lurking within?
Well, a chest X-ray would show you our handiwork. We like to get deep into the lungs, inflame one or two lobes so your body will react by solidifying the lobe - which starves you of oxygen. Ha!
You may try to track us indirectly by looking for the antibodies you clueless folks try to form against us. You may also find us directly using the polymerase chain reaction (PCR) to look for our RNA.
PCR? How does that expose your royal derrier?
Actually, you will need RTPCR, or reverse transcription PCR, to look for us RNA viruses, not plain vanilla PCR which looks for DNA. An enzyme called reverse transcriptase is used to generate complementary DNA (cDNA) copies of our RNAs.
The cDNAs are then cloned by using an enzyme called DNA polymerase, which unzips the DNA helix and makes copies of it.
This takes two minutes, and each cycle is repeated 30 times with each new copy becoming the template. After 30 cycles, there are one billion copies of the first DNA molecule. That way, there's enough DNA for you to detect. Otherwise, looking for a few DNA molecules will be like looking for a needle in a haystack.
Because you need to set different temperatures for each stage, the process actually takes three hours.
So PCR is like a genetic printing press, making repeated copies inexpensive and accessible. Why aren't our doctors using it yet?
The kit is now as big as a microwave oven. The small kits for other RNA viruses don't work for us, I'm happy to report.
Once you have chip-sized devices that look specifically for our RNA, you'd be able to have a diagnosis on the spot. But that's going to take time.
PHANTOMS OF THE OPERA
THAT'S depressing. We don't know how to find you and we can't knock you out. We should just keep you out then. Are face masks and respirators any good?
Not the paper masks sold at hardware stores. They let in such big pieces they're only good for sweeping out the garage or mowing the lawn.
Surgical masks trap particles bigger than 4,000 nm (or nanometer, a thousandth of a millimeter) - not useful when we are only 80-160 nm in size.
Now, the N95 mask keeps out particles larger than 300 nm, so it can get those of us wrapped in moisture bubbles while its polypropylene fibres generate static electricity that grabs small particles.
But don't forget that any filter eventually clogs, so you have to replace the mask, say, every four hours. The smallest leak would also render it useless, whether from a poor fit or even a crack.
So that's why so many health-care workers get infected despite donning masks and protective gear?
Yes, but these valiant souls are exposed to us for hours on end and probably come into contact with bodily secretions directly too. Ideally, they should have a full-face respirator worn with a sack suit like those which scientists in the movies put on to go into Ebola-stricken areas.
They must also pay attention to how they remove their gloves, boots and suits after decontamination.
Decontamination can be incomplete, so they may catch us who are still hiding on the suit as they are removing it.
Sometimes, viruses can also be forced out in the pressurised air while doctors are inserting a tube into a patient's lungs. That's how Dr Ong Hok Su, who became the eighth person to die here, was probably infected.
Are lab workers at high risk handling samples from Sars patients?
It's a good idea to treat us with respect, since you don't know all that much about us. Perhaps work should be done in a BL3 - biological safety level 3 - lab. Our intelligence says your Defence Science Organisation (DSO) has one.
HAPPILY EVER AFTER?
ERR, I have a stupid question. Are those who die because of you critters still infectious?
Moron. All viruses need living cells. We remain infective outside the live human body for only a short time.
Your people have ordered mandatory cremations perhaps because they worry about us somehow getting back into living tissues.
Any last words?
Yes. A tip. As you begin to see fourth- and fifth-order cases, your doctors must be extra vigilant, as the links to known cases will become fainter. In fact, you have just picked up the first atypical case in Singapore General Hospital.
Doctors should now err on the side of caution, testing blood oxygen levels and doing chest X-rays, even for cases that aren't clear. And that's all I'll say.
With a flourish, the Czar was gone... on to some dastardly deed, no doubt.
(Technical details in this story were compiled from medical journals and texts.)
(Andy Ho is a senior writer with The Straits Times.)
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