Progesterone, & HIV
By Bob Lee <>
Bovine-visna virus, now called "Bovine Immunodeficiency Virus" (BIV) is the closest relative to HIV that is not a primate lentivirus. All lentiviruses closer to HIV exist in simian hosts through the "Simian Immunodeficiency Virus" (SIV). The closest HIV relative in primates is
SIVcpz (chimpanzee SIV).
To understand the construction of these lentiviruses (and hence to possibly discover more about HIV's operations and affinities), it is useful to examine different pieces of these lentiviruses and, in this case, as BIV is the closest non-primate lentivirus like HIV, it is examined in this short piece.
The parts of the BIV lentivirus of interest are called "env", "gag", and
"pol." The "env" gene is the outside covering of the BIV retrovirus, i.e., the spikey covering. The "gag" gene of BIV encodes nucleocapsid of BIV, i.e., the icosohedral-shaped package covering containing the "guts" (or "pol") of the BIV retrovirus. Therefore, we will examine these 3 parts to get an idea of the construction of BIV, HIV's closest non-primate relative lentivirus. This first installment deals only with
BIV's envelope.
The envelope of BIV ("env") contains amino-acids that code progesterone receptors. Progesterone is a hormone found in all higher-order animals like chickens, mice, cats, primates, and humans. Progesterone is a hormone used, in human females, for example, in combination with estrogen to regulate the human female's monthly menstruation. Progesterone and estrogen are considered to be the "female" hormones just as testosterone and androgens are considered to be the "male" hormones in humans. Nevertheless both sexes contain all 4 of these hormones.
A lentivirus bearing progesterone receptors on its envelope will be attracted to cells displaying progesterone on their cell surfaces. Think of it as a lock and key. Progesterone receptors will lock with progesterone-displaying cells. Hence, we see in this way how the BIV lentivirus docks with cells in the infection process. What cells display progesterone? In human females, for example, vaginal wall cells
display progesterone. Many other mucous-membrane cells also display progesterone in both the female and male sex of different higher-order species.
What does this tell us regarding HIV (Human Immunodeficiency Virus)? Isn't HIV's envelope very different from BIV's? Is it possible that BIV's can infect humans? Many questions...
HIV is known to "dock" with cells expressing a "CCR5" on cell surfaces among other chemicals. CCR5 is "cell cytokine receptor #5." Is there a
relationship between BIV's progesterone receptors envelope and HIV's gp120 (glycoprotein 120) that is HIV's envelope? Yes there is. Examination of CCR5 amino acids compared to progesterone receptor amino-acids shows there is some similarity between the two. There is some type of progesterone activity going on in both BIV's cell docking and HIV's cell docking mechanisms.
Recent studies show that both monkeys and women who have high levels of progesterone are at higher risk for HIV infection than monkeys or women who have lower levels of progesterone [1]. Recent studies also show that, in some caucasians of northern European descent, a CCR5 genetic condition exists (called "CCR5 32-deletion") which results in extreme resistance to HIV infection. There is an estimated 1% to 10% of the northern European caucausian population that has this genetic condition rendering them impervious to normal routes of HIV infection. All efforts to locate this CCR5-32 deletion gene in non-whites have failed. None of the non-white populations throughout the world have this genetic
resistance to normal routes of HIV invasion.
We might reason, then, as the CCR5 docking mechanism of HIV is very similar to BIV's progesterone receptor docking mechanism and as there is
a relationship between progesterone receptor construction and CCR5 construction, that there must be some progesterone receptor mutation which, being related to CCR5, may make persons resistant to HIV infection through normal routes. Logic would suggest that as progesterone levels increase in monkeys and women resulting in their increased risk for HIV infection that an anti-progesterone may decrease the risk of infection by HIV. The anti-progesterone would, hypothetically, interfere in HIV's docking mechanisms on cells in the infection process.
What is that anti-progesterone? Is this anti-progesterone being produced in caucasians with the CCR5 32-deletion gene? No one knows. More importantly not one single study has been published concerning this
In females, both estrogen and progesterone operate in tandem to regulate
the females menstrual cycle. Progesterone is produced in the female in an organ called the "corpus leuteum" (which is a follicle in her ovary that has released an egg). When both estrogen and progesterone levels drop in the female, she has her "period." When estrogen and progesterone levels are out of balance, the female may have transient mood disorders ("premenstrual syndrome" PMS) or, after giving birth when
these hormones are out of balance, she may have "post-partum depression." We therefore see an intimate relationship between estrogen
and progesterone. Perhaps estrogen, which men have in small quantities,
is an anti-progestrone?
In North America we see the preponderance of HIV cases happening in males as well as a disproportionate rate of infection among non-whites. If you are a non-white male in North America you have an extremely disproportionate risk of contracting HIV as compared to caucasian females. In the above material, we have seen the likelihood of a possible relationship between progesterone, progesterone-receptors, and CCR5 (in which some caucasians have a 32-deletion defect conferring HIV resistance). These data suggest that HIV's method of operation (and generalizing from study of BIV's envelope), is to capitalize on docking with progesterone-displaying cells (through CCR5 docking) in a manner quite similar to BIV (progesterone receptor docking). Males have progesterone as one of their sex hormones in small proportions (along with small proportions of estrogen and major proportions of testosterone
and androgens). Could it be possible that the reason North American black males are disproportionately infected with HIV as compared to causasians or females is this progesterone/CCR5 gene interaction? No one knows. No one has even looked as of August, 2000.
Could an anti-progesterone medication be useful in conferring HIV resistance to infection in those populations that do not have the CCR5 32-deletion genetic defect? Could estrogen be the anti-progesterone? No one knows. No one has even looked as of August, 2000.
Finally, to conclude this small article examining BIV env in relationship to HIV, the progesterone receptors in BIV env are NOT bovine progesterone receptors as you would expect. Rather, these progesterone receptors in BIV's envelope protein are noted in protein databanks to be chicken, rat, and human progesterone receptors. Now I ask you, how could a bovine lentivirus, alleged to have a history of some thousands of years, have chicken, rat, and human progesterone receptors on its envelope and not bovine progesterone receptors???
Bovine-visna (BIV) was first reported in the literature circa 1970 associated with the work of Van der Maaten et al. from Iowa State University's school of veternarian science. [2] In 1968 both bovine (cow) and porcine (pig) cells had been infected with Maedi-visna virus (a lentivirus of sheep) in the laboratory [3] resulting in a bovine-visna virus. In 1978 human cells were infected with BIV in the laboratory.[4].
There are further interesting comparisons to made concerning the similarity in structure of Bovine Immunodeficiency Virus and HIV. Stay tuned. More info at or at
[1] Marx PA, Spira AI, Gettie A, Dailey PJ, Veazey RS, Lackner AA, Mahoney CJ, Miller CJ, Claypool LE, Ho DD, Alexander NJ. Progesterone implants enhance SIV vaginal transmission and early virus load. Nat Med 1996 Oct;2(10):1084-9
Mascola JR, Stiegler G, VanCott TC, Katinger H, Carpenter CB, Hanson CE,
Beary H, Hayes D, Frankel SS, Birx DL, Lewis MG. Protection of macaques against vaginal transmission of a pathogenic HIV-1/SIV chimeric
virus by passive infusion of neutralizing antibodies. Nat Med 2000 Feb;6(2):207-10
[2] Boothe AD, Van der Maaten MJ, Malmquist WA. Morphological variation of a syncytial virus from lymphosarcomatous and apparently normal cattle. Arch Gesamte Virusforsch 1970;31(3):373-84
[3] Harter DH, Hsu KC, Rose HM. Multiplication of visna virus in bovine and porcine cell lines. Proc Soc Exp Biol Med 1968 Oct;129(1):295-300
[4] Georgiades JA, Billiau A, Vanderschueren B. Infection of human cell cultures with bovine visna virus. J Gen Virol 1978 Feb;38(2):375-81

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