HIV The smartest virus in history?
Globe and Mail:
August 12, 2006: CAROLYN ABRAHAM, Medical Reporter
Tracing the origins of HIV has been a Herculean task and
often not a glamorous one. Most recently, it involved the serious scrutiny
of 599 samples of ape feces.
But after two decades of work, scientists have slowly pieced together a
biography of the human immunodeficiency virus — where it was born, what its
ancestors were and possibly how it grew up to be the mass murderer of the
Not since the Middle Ages has one virus cut such a long, wide swath through
humanity. More than 25 million people have died since HIV was first
recognized in 1981. More than 40 million have been infected. Some experts
predict that by 2020, AIDS could prove to be the most destructive pandemic
in history. Yet in all likelihood, HIV was not the first virus of its kind
to infect humans, and scientists suspect it will not be the last.
The closest ancestor of the AIDS virus lived in West Africa's chimpanzees
for thousands of years, and chimps have long been on the menu of human
hunters in that corner of the world.
HIV is believed to have been killing people in Africa for roughly 50 years
before the world knew the virus existed. Yet scientists have since
discovered the pandemic virus was one of three types of HIV that jumped to
humans around the same time. But due to a fateful confluence of events and
genetic accidents, only the one — HIV-1, group M — gave rise to the global
scourge that continues to stump medical science.
The king of freeloaders
HIV belongs to a group of pathogens known as retroviruses. They were once
considered rare, medical curiosities and only late in the 20th century were
they discovered to actually infect humans.
They have no ability to replicate outside of a host cell and they carry
their genetic material not in the double-stranded code of DNA, but the
single strand of RNA that makes proteins.
HIV is a retrovirus with just nine genes tucked inside a round protein
envelope. Magnified, it looks a little like the wheel of a ship, circular
with spikes radiating from its surface. The virus makes its way through the
world on rivers of bodily fluids, striking humans at their most intimate
points of contact — sexual intercourse, childbirth, breastfeeding. Tainted
blood and intravenous drug use have also been sources of transmission, and
HIV has developed uncanny methods to spread itself. Outside of a human host,
"It's a bit wimpy that way," said Richard Harrigan, director of the research
laboratories at the B.C. Centre for Excellence in HIV/AIDS. A few hours
outside of a human body and the virus is no longer infectious, he said; nor
can it be easily grown in a lab dish.
But inside a T cell, the story is dramatically different. T cells are
lymphocytes, or white blood cells, that orchestrate the body's ability to
fight infection. The HIV attacks them, specifically a type known as CD4,
like a guided missile.
The virus breaks in with its own set of keys and slips into the host cell
like an unwanted guest. Then it settles down to become the king of
freeloaders, injecting its own genetic material into the DNA of its host and
making an HIV factory of the very cell that was designed to kill it.
New viruses eventually burst out of the host cell to wreak fresh rounds of
destruction. "Integrating itself directly into the DNA of the host means you
can't get to it easily to cause its destruction without the risk of damaging
the host's cell," Dr. Harrigan said. "It also makes lots and lots of copies
of itself every single day."
How many copies?
"Oh," he said, "about 10 billion."
It started with chimps
Chimpanzees had long been the suspected source of the AIDS pandemic. HIV
bears a close genetic resemblance to a chimp infection known as simian
immune deficiency virus, or SIVcpz.
But it was only this spring that an international team of scientists, led by
Beatrice Hahn at the University of Alabama, was finally able to confirm that
this chimp virus exists in the wild and that it was indeed the progenitor of
Dr. Sharp, who, along with researchers in France and Cameroon, has worked
with Dr. Hahn's group since 1991, said the study, published in Science, was
a long time coming. Collecting blood from wild apes was considered too
invasive and dangerous, so researchers spent years developing molecular
tests to run on chimp droppings instead. The samples, amassed with the help
of trekkers, were scooped up from 10 remote areas of forest in central West
Africa and preserved in tubes.
Molecular tests on the samples were able to determine the species and sex of
the animal to whom it belonged, whether it carried antibodies for an SIV, or
genetic material of the virus itself. The results showed the virus most
closely related to the HIV-1 pandemic strain was indeed the SIVcpz strain.
Researchers believe it jumped to a single human from a chimp in southeast
Cameroon about 70 years ago.
Scientists can estimate the date because viruses are believed to mutate at a
fairly constant rate. By comparing the oldest known HIV strain with its
progenitor chimp virus, they can clock when the two diverged and one crossed
the species barrier.
"The only missing part of the story is from one person [contracting it]
around about 1930 or a little earlier, getting infected with the virus and
then getting it down to Kinshasa," Dr. Sharp said.
Kinshasa is considered ground zero of the AIDS pandemic, since the HIV-1
subtypes there are older and more diverse than anywhere else in the world.
"We would imagine that this virus has been transmitted down rivers ending up
in Kinshasa, known as Leopoldville in those days," Dr. Sharp said. "The
virus needed to get to somewhere like that, it needed to get to a big city
before it could really get started as an epidemic."
The earliest known case to come from the continent would not, however, be
diagnosed for several decades. A blood sample taken in 1959 from a Bantu man
participating in a medical study in Kinshasa was found in the 1980s to be
HIV positive. By then, the virus had the world's attention.
|Mass cellular slaughter
Ask where the AIDS virus ranks among its peer pathogens and scientists
rarely hesitate: "In terms of its smarts, it's right up at the top," said
Mark Wainberg, director of the McGill University AIDS Centre. "Not only does
it know how to escape from everything we throw at it, but if you're the
virus, your main objective . . . is to survive and spread yourself to as
many people as possible. You don't do that if you're a virus that kills your
host within a week. If you want to be efficient at spreading yourself, you
want your host to stay alive for a number of years and remain infectious
throughout that time."
In its early stages, HIV triggers a mass slaughter of its host's T cells,
most notably in the gut. Tissues that line the intestines contain more
lymphocytes than any other single site in the body.
"This is the largest organ in the body in terms of the immune system. If not
the heart, the soul of the immune system," Dr. Wainberg said.Scientists have
found it can take up to four months before the immune system kicks in to
produce antibodies that can be detected in a blood test.
"The immune response you see with HIV is somewhat slower than what you see
with lots of other infectious agents," Dr. Wainberg said. "Probably because
the immune system is overwhelmed, partly because the virus is infecting the
very cells that we need to respond quickly. It's a very insidious virus."
The earliest phase of infection is also the most contagious. With no
immediate immune response, the patient's "viral load" — the medical term for
the number of HIV particles in a given volume of blood — soars.
"Before a person knows they are infected, they are at their most infectious
and because they don't know it, they are not practising safe sex," Dr.
Once the immune system responds, the viral load drops, reducing the risk of
transmission. The viral load can remain low and stable for several years.
But that number will eventually rise again, resulting in big losses of T
cells that can lead to acquired immune deficiency syndrome without effective
AIDS leaves the body with an immune system so crippled that opportunistic
infections, such as pneumonia, tuberculosis and certain cancers pose a
sudden and serious threat. Yet one intriguing hallmark of HIV in humans is
how few T cells actually become infected. "At any given time, it's less than
1 per cent," Dr. Wainberg said. "Yet the number of losses of T cells can be
Dr. Wainberg said the accepted theory is that HIV not only kills the cells
it directly infects, but that infected cells secrete a substance toxic to
other, uninfected T cells. This in turn triggers the body's own killing of
these other cells.
The HIV-like virus chimps carry is a descendant of two other ape viruses —
one that infected red-capped mangabeys and another that infected
"The ancestors of those two monkey viruses have recombined to form what is
now the chimp virus [that gave rise to HIV]," Dr. Sharp said.
No one knows exactly when chimps contracted it, but it's estimated to be
anywhere from 70,000 to 1.5 million years ago. Neither can anyone say how
the virus first affected chimpanzees. It may well have wiped out all chimps
without a natural resistance, Dr. Sharp said. "We know at the moment, these
viruses don't cause any illness in chimps. They get infected, but they never
get to the stage of deteriorating.
"The real problem with AIDS is that you are destroying your own T cells, and
when you've destroyed your own T cells you are susceptible to infection. If
somehow the immune system can avoid recognizing the virus and destroying
them, you may be okay."
The chimp's immune system, for example, has somehow learned to simply ignore
the infection, Dr. Sharp said.
Dr. Sharp has lately been studying the three separate HIV-1 groups that
jumped from chimps to humans on separate occasions. His hope was to find
something that distinguished them from the chimp virus that spawned them.
"The logic of our ongoing analysis was to say, well if we find a site in a
gene which is the same in each of the HIV groups, but different in all the
chimp viruses, then those are changes that have occurred in all of the three
groups leading to HIV," he explained, "that would be too big of a
coincidence for it to just be an accident. It must be something that has
been selected for as the virus adapts to its new host."
The hunch bore fruit. Dr. Sharp has located a single chemical change in a
protein important to the core matrix HIV-1. The change is there in all three
groups of the human form of the virus, but not the chimp virus.
What's more, Dr. Sharp learned that a research project 10 years ago showed
that when chimps are infected with HIV-1, the virus does not fare well. But
over time, the virus adapts and the protein switches back to the original
form it originally had in chimpanzees.
"This tells you it's important for the chimp virus to have it one way, and
to move into humans to have it this other way."
Looking to the future
People often ask Dr. Sharp how it could be that a virus like HIV could go
undetected for half a century, infecting one person in 1930 to 40 million by
2000. But he's done the math, and he feels numbers as well as geography
"If you did just the simplest epidemiological plot . . . you see only about
2,000 people infected in 1960. . . . Even by 1980, you are only getting up
to a million people.
"It takes a long time for the numbers to build up. It really is not at all
surprising that nobody knew about this virus in 1960; there just weren't
that many people infected and they were all in Central Africa.
"So it's no surprise to me that the virus went undetected for so long."
What concerns him more is that about 30 species of monkeys in Africa carry
simian immune deficiency viruses. "With continued exposure to these viruses,
more of them could jump into humans," he said.
"There is an ongoing risk."