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Origin of HIV

Greg Tobin tobin at fcs260c.ncifcrf.gov
Fri Jul 8 14:43:45 EST 1994


Mike asks:

I would appreciate it if some of the virologists in this newsgroup would
ehyeball the following (abbreviated) theory about HIV development.
Not being a virologist or medical person, I wanted to know how possible
this concept of HIV development was.

The theory that AIDS originated in the laboratory has been
circulating in Europe, particularly in West Germany, since late
1986.

The theory hinges on the claim that the AIDS virus (HIV) is
virtually identical to two other viruses:  Visna, which causes a
fatal disease in sheep but does not infect humans, and HTLV-I
(Human T-Cell Leukemia Virus), which infects humans but is seldom
fatal.

	- It is true that HIV and Visna are both lentiviruses and have
	- LTR, gag, pol, env, vif, rev, and vif.  However, HIV has number
	- of other genes that may not be present in Visna (vpu, vpr,
	- nef).  Moreover, visna antigens (Gag and Env) do not share
	- epitopes with HIV (as judged by RIP and Western).  Other
	- lentiviruses such as BIV, and SIV share antigentic cross-reactivity
	- with HIV in some Gag proteins (CA, NC).  Anther major difference
	- is the obvious species tropism.  Visna infects goat and sheep
	- cells, HIV infects primate (largely human) cells.
	- HTLV-1 belongs to the group (still unnamed?) that includes
	- BLV.  Very little homology exists between the two most highly
	- conserved protiens (RT) of HIV and HTLV.  HTLV also has a 
	- different gene structure.  If you look at TEM, HTLV particles
	- look like hollow balls in cross-section; HIV particles have
	- a condensed (rod- or cone-shaped) core structure inside the 
	- electron-dense ball.
Prof. Jakob Segal, the author of the theory, says that structural
analysis using genome mapping proves that HIV is more similar to
Visna than to any other retrovirus.  The portion (about three
percent) of the HIV genome which does not correspond structurally
to Visna corresponds exactly to part of the HTLV-I genome.

	- Not true.  Compare the sequences yourself. Pull them out
	- of GenBank or the Los Alamos database (ftp atlas.lanl.gov)
	- and align them with one of the Staden or UWGCG programs.

He notes that the symptoms of AIDS are consistent with the
complementary effects of two different viruses.  AIDS patients who
do not die of the consequences of immune deficiency show the same
damage to the brain, lungs, intestines, and kidneys that occurs in
sheep affected with Visna.  Combining Visna with HTLV-I would
allow the virus to enter not only the macrophages of the inner
organs but also the T4 lymphocytes and thus cause immune
deficiency, which is exactly what AIDS does.

	- A change in the promoter (located in the LTR) can cause
	- changes in cell tropism.  Visna is particularly noted
	- for producing neurological disease in Icelandic sheep
	- (Andresson et al, J. Virology 193:89-105, 1993).  HIV can
	- also produce neurological disease.  However, combining two
	- viral promoters means removing desireable sequences from 
	- one and inserting into another.  These sequences have only
	- recently been identified.  Usually the insertion of one sequence
	- will result in changes of the others, so this would take a 
	- lot of effort using techniques not readily available ten years
	- ago.
As further evidence that HIV is a construct of Visna and HTLV-
I, Segal cites studies which show that the reverse transcription
process in HIV has two discrete points of peak activity which
correspond, respectively, to those of Visna and HTLV-I.

	- I think you are referring to the Mg++-dependent activity (peaks
	- about 10 mM) and Mn++-dependent activity (peaks around 1mM) for
	- HIV.  This is consistent with visna, but not HTLV.

AIDS is thus, according to Segal, essentially a variety of Visna.
This has important implications for research, since a cure or
vaccine might be found sooner by studying Visna in sheep than by
concentrating, as at present, on monkeys.

	- This is an excellent point.  I agree that we should study other
	- related viruses and their pathogenesis.  For simplicity, we
	- could study lentiviruses that infect small animals (BIV-rabbits,
	- FIV-cats).  However, SIV is much closer to HIV than any other
	- lentivirus.  This explains why there is such a large amout of
	- effort in this direction.  
	- Because of similarities between HIV and other lentiviruses,
	- more support should be channeled into the study of the other 
	- lentiviruses for correlative purposes.

	- The above remarks are intended to reflect my personal opinions,
	- and do not necessarily correlate with those of any institution
	- or employer affiliated with me.

-- 
Greg Tobin, Ph.D.                        tobin at lcms-1.ncifcrf.gov
LCMS 
PO Box B
Frederick, MD 21702



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