JIM@AUVM.AUVM.EDU (Jim McIntosh) (06/21/89)
Infectious Disease's UPDATE
CONTACT: Laurie K. Doepel
301-496-5717
Wednesday, May 31, 1989
NEW DATA LINKS HIV-2 TO MONKEY VIRUS
Eight years into the AIDS epidemic, researchers are still
baffled by the question, where did the AIDS viruses come from?
The disease is now known to be caused by two human
immunodeficiency viruses, HIV-1 and HIV-2: the former, the cause
of most AIDS cases worldwide, appears to have spread out from
central Africa, while the latter has so far been confined mainly
to West Africa nd the islands off its coast.
In this week's issue of the journal Nature, scientists
present new evidence that a virus isolated from a species of West
African monkey may have successfully infected humans 20 to 40
years ago and subsequently evolved into HIV-2.
The study, funded by the National Institute of Allergy and
Infectious Diseases (NIAID), was conducted by Drs. Vanessa M.
Hirsch, Robert A. Olmsted, and Philip R. Johnson of Georgetown
University; Dr. Michael Murphey-Corb of the Delta Regional
Primate Research Center at Tulane University; and Dr. Robert H.
Purcell of NIAID.
The focus of their study, a virus known as SIVsm (simian
immunodeficiency virus from sooty mangabey), infects wild and
captive sooty mangabey monkeys and was first isolated by Murphey-
Corb in 1986. Johnson and Hirsch led the collaborative effort to
molecularly clone and sequence the virus. With this new
information, they constructed an evolutionary tree of the several
known primate immunodeficiency viruses. This tree showed SIVsm
and HIV-2 to be closely related.
Of nearly equal importance, SIVsm is the first
immunodeficiency virus known to infect wild monkeys in West
Africa, the area where HIV-2 is endemic. The presence there of
such a closely related virus in wild monkeys does not prove that
the virus crossed over from monkeys to humans. Given the two
species' close association, however, it makes this scenario
highly plausible.
West Africans keep sooty mangabeys as pets, although they
also eat them and sell them in the markets. The monkeys live
inside their homes, much as dogs do here. According to the
scientists, the most likely way the monkey virus could have
infected humans was via a bite. That, they say, could easily
have been a one-time event: somebody was bitten, and the virus
found a favorable environment and multiplied in that person, who
then passed it on to others.
HIV-2's domain remains West Africa--particularly Guinea-
Bissau, Senegal, the Cape Verde islands, and Gambia. In certain
of these area, the infection rate appears to be quite high.
HIV-2 infection has also been recently reported in some countries
of South America, and two cases of HIV-2 have been documented in
the United States, but these cases can be linked to immigration
from West Africa. Transmission of HIV-2 occurs in the same way
as HIV-1--sexually, through infected blood or blood products, or
perinatally--but some scientists believe HIV-2 is less virulent
than HIV-1 because fewer infected people have become sick.
Hirsch and her colleagues also found that SIVsm closely
resembles SIV isolated from a species of Asian monkeys, macaques
acquired the virus from another monkey species with which they
once shared housing. Because SIVmac and SIVsm closely resemble
one another, sooty mangabeys are now the suspected source of that
cross-species infection.
Scientists know that immunodeficiency viruses can cross
species, as proved by the fact that HIV-1 grows in chimpanzees
and HIV-2 grows in baboons and macaques. Dr. Russell F.
Doolittle, professor in the Center for Molecular Genetics at the
University of California, San Diego, explains how this happens.
In a "News and Views" commentary published in Nature to accompany
the Hirsch article, Doolittle writes, "There are some remarkable
aspects to all this. Quite apart from the astonishing ease with
which horizontal retrovirus infection appears to occur among non-
human primates that are housed together...the most fascinating
aspect of these heterologous involvements is that the primary
hosts all appear to be healthy. For example, the mangabeys that
furnished the virus for the Hirsch study were all perfectly
healthy. When the virus was injected into macaque monkeys,
however, the animals rapidly succumbed to a severe illness,
ultimately dying of opportunistic infections."
Doolittle clarifies this mystery by distinguishing the
lifestyles of exogenous and endogenous retroviruses, which can
appear in multiple copies throughout the host's DNA, are usually
benign and often defective. "In some cases it has been shown
that these multiple copies have been frozen in place for millions
of years." Endogenous retroviruses can play a protective role in
the host, somehow making the host resistant to viruses of other
animals. "Consider, for example," he writes, "what happens when
domestic cats are exposed to the baboon endogenous virus. If the
cat is carrying the closely related feline leukemia virus in its
germline as a consequence of previous ancestral exposure, the cat
is not afflicted. Cats not carrying the virus in their germline
are smitten, however."
Genetically, HIV-2 more closely resembles SIV than HIV-1,
and the possible find of a monkey virus origin for HIV-2 is not
surprising. Proving the direct connection between HIV-2 and
SIVsm, though, will be very difficult. According to Johnson,
"The simian virus we analyzed has been in sooty mangabeys in
North America for more than two decades. The HIV-2 isolates
reported to date also likely represent 20 or more years of
evolution and adaptation in humans in West Africa. Taking both
these facts into consideration, the degree of similarity between
these viruses is remarkable, and argues that they evolved from a
common ancestor in the not-too-distant past." The scientists are
now trying to obtain samples of SIV from West Africa.
"SIV from sooty mangabeys: An African non-human primate
lentivirus closely related to HIV-2," Vanessa M. Hirsch, Robert
A. Olmsted, Michael Murphey-Corb, Robert H. Purcell, and Philip
R. Johnson. Nature 339, 389 (1989).