From the archive, originally posted by: [ spectre ]

Science 22 June 2007:
Vol. 316. no. 5832, pp. 1756 – 1758
DOI: 10.1126/science.1140579

Restriction of an Extinct Retrovirus by the Human TRIM5{alpha}
Antiviral Protein
Shari M. Kaiser,1,2 Harmit S. Malik,3 Michael Emerman2,3*

Primate genomes contain a large number of endogenous retroviruses and
encode evolutionarily dynamic proteins that provide intrinsic immunity
to retroviral infections. We report here the resurrection of the core
protein of a 4-million-year-old endogenous virus from the chimpanzee
genome and show that the human variant of the intrinsic immune protein
TRIM5{alpha} can actively prevent infection by this virus. However, we
suggest that selective changes that have occurred in the human lineage
during the acquisition of resistance to this virus, and perhaps
similar viruses, may have left our species more susceptible to
infection by human immunodeficiency virus type 1 (HIV-1).

Ancient trade-off may explain why humans get HIV
Roxanne Khamsi  /  21 June 2007

A protein that protected our human ancestors against a virus that
ravaged other primates may now be responsible for our susceptibility
to HIV, a new study suggests.

The discovery could help scientists predict which viruses found in
other species are most likely to cross over and lethally infect

The idea that early humans had an immune system that differed from
other primates first came about after biologists sequenced the chimp

The chimp sequence contains 130 copies of a virus called Pan
troglodytes endogenous retrovirus, or PtERV1. Retroviruses often have
the ability to insert themselves into an organism’s DNA. But PtERV1 is
completely absent from the human genome.

Reviving ancient life

Studies have also shown that the human version of an antiviral protein
called TRIM5-alpha differs dramatically to the version of this protein
found in other primate species. TRIM5-alpha offers immune protection
by binding to virus-containing capsules inside cells and prompting
their destruction.

Michael Emerman at the Fred Hutchinson Cancer Research Center in
Seattle, US, and colleagues decided to test whether our unique version
of TRIM5-alpha could explain why PtERV1 did not invade our genome.

The team generated TRIM5-alpha from human, chimp and gorilla genes in
order to see how well various versions of the protein protected
against PtERV1 in cat cells grown in a laboratory dish.

There was one problem though: active versions of PtERV1 no longer
exist and the copies of this retrovirus found in primate DNA are
woefully degraded.

So Emerman’s team looked for commonalities among the chimp versions of
the virus to partly reconstruct the ancient form of PtERV1. From this
ancient sequence they produced part of the PtERV1-containing capsule,
and attached it to a harmless mouse virus.

HIV vulnerability

About 4% of the cat cells exposed to this resurrected PtERV1 capsule
combination became infected within a day. And those cat cells that
also contained the gorilla version of TRIM5-alpha did no better.

But human TRIM5-alpha protected the cat cells, leaving them 100 times
less susceptible to PtERV1 infection – only 0.04% of the cells became

On the flipside, Emerman notes that the human version of TRIM5-alpha
does not recognise the capsule containing HIV inside cells, whereas
other primate versions of this protein can.

Non-human primates do not normally get infected with HIV. So he
speculates that the same attributes of TRIM5-alpha that make it
effective against PtERV1 might explain why it cannot bind and destroy

Emerman suggests that monitoring how well the human version of TRIM5-
alpha protects against viruses related to HIV, could help scientists
predict which pathogens have the potential to cross into our species
from other primates.

Journal reference: Science (DOI: 10.1126/science.1140579)


FHCRC Director: Michael Emerman, PhD
Phone Number: 206-667-5058
E-mail: memerman [at] fhcrc [dot] org

The Emerman lab studies the regulatory and structural genes of the
human immunodeficiency virus (HIV) in order to understand the
molecular basis for its replication and pathogenic properties. Because
the virus requires host cell proteins to complete nearly every step of
it lifecycle, much of our focus is on identifying and characterizing
host cell functions that are modified or utilized by viral proteins to
serve specific functions for viral replication.

Shari M. Kaiser,1,2 Harmit S. Malik,3 Michael Emerman2,3*

1 Molecular and Cellular Biology Program, University of Washington,
Seattle, WA 98195, USA.
2 Division of Human Biology, Fred Hutchinson Cancer Research Center,
Seattle, WA 98109, USA.
3 Division of Basic Sciences, Fred Hutchinson Cancer Research Center,
Seattle, WA 98109, USA.