Oldest Nearly Complete HIV Genome Found In Forgotten Tissue Sample

October 1, 2020

A new study has found the oldest known almost complete genetic sequence of an HIV
strain that spreads worldwide in tissue samples from the Democratic Republic of Congo
(DRC).

The tissue sample was collected and preserved in 1966, making this HIV sequence 10
years older than the previous oldest genome, from a blood sample collected in the DRC
in 1976. Genetic sequences like this – from before the discovery of the virus that
causes AIDS in 1983 – help determine the timing of the virus’ genetic mutations. These
mutations, in turn, help scientists track the spread of the virus and how long HIV has
been spreading in humans.

In that sense, the new gene sequence is “very reassuring,” said Sophie Gryseels, co-
author of the new study and a postdoctoral researcher in evolutionary and computational
virology at the Catholic University of Leuven (KU Leuven) in Belgium. She told Live
Science that the sequence fits well with the researchers’ previous understanding of
when HIV emerged.

“It’s good to know because it means that the evolutionary model we’ve been applying to
the viral sequence works well,” Gryseels said.” We don’t have any big surprises.”

The emergence of the virus
Based on genetic sequencing of viral samples, scientists believe that HIV, or human
immunodeficiency virus, first found a foothold in humans when it spread from
chimpanzees to Central Africa sometime in the early 20th century. There are multiple
strains of the virus, but the one responsible for 95 percent of the world’s cases is a
subgroup called the HIV-1 M group. Since the beginning of the epidemic, more than 32
million people have died from AIDS, the disease caused by HIV.

Many of the early dynamics of the disease remain mysterious from the time HIV-1 began
to spread in humans until the virus was discovered, at least 80 years ago. Mathematical
models of how quickly the virus mutates imply when HIV begins to spread from person to
person, and transmission eventually turns into a pandemic. But a big question is when
and why HIV-1 group M became so successful at infecting people effectively enough to go
global.

Part of the problem, Gryseels said, is that models that have done a good job in recent
years of calculating the rate of viral change have become less reliable over longer
time scales. Part of the reason is that genetic information is lost over time. Through
natural selection or simple luck, strains die off, leaving no trace of their presence
on the genomes of currently circulating viruses.

For this reason, discovering an ancient strain of virus is a bit like discovering
Archaeopteryx for paleontologists; it’s the missing piece of the puzzle that helps fill
in the gaps in evolutionary change.

Ancient HIV
Gryseel participated in an ongoing project led by University of Arizona evolutionary
biologist Michael Worobey and, along with other colleagues in Belgium, the United
States and the Democratic Republic of Congo, analyzed 1,645 biopsy specimens collected
in Central Africa between 1958 and 1966 to diagnose medical conditions. These biopsy
specimens were preserved in chemical formalin and then embedded in paraffin. The
researchers used a very sensitive PCR method (similar to the method used to detect the
new coronavirus SARS-CoV-2 in a nasopharyngeal swab) to look for traces of the HIV
genome. They found only one. A sequence from a lymph node biopsy of a 38-year-old man.

There are older HIV fragments out there, one from 1959 and one from 1960, also from the
Democratic Republic of Congo. But those fragments aren’t as complete, so they don’t
provide as much information about how the virus has mutated.Gryseels said those
fragments are also from different subtypes of HIV, suggesting that the virus had been
circulating in humans for some time before the 1950s.

Researchers will continue to look for old HIV genomes in tissue samples from long ago,
Gryseels said. It would be ideal to find more samples from the 1950s or 1960s to
confirm the results, she said. The next goal is to figure out when HIV-1 transitioned
to an accelerated epidemic. It’s possible that some changes in HIV-1’s genome made it
more efficient, Gryseels said, but it’s more likely that social changes made the
difference.The early 20th century saw a rapid rise in urbanization in Central Africa.
Between the 1910s and 1950s, public health campaigns expanded treatment for diseases
ranging from sleeping sickness to malaria and syphilis. But many of these campaigns did
not properly sterilize needles, which could have allowed HIV to spread
widely.Decolonization in the 1960s may also have led people to move around or behave
differently, which could have helped the virus spread to new populations or spread more
quickly.

“If we can better understand the timeline of when this expansion occurred, we can weigh
these different hypotheses more effectively because they occurred at different times,”
Gryseels said.