In the early 1980s, when AIDS first erupted among Haitians, drugusers and gay men, most heterosexuals were supposedly protectedfrom HIV infection. The reasoning ran that anal intercourse practicedby male homosexuals transmitted the virus via breaks in delicate skin,as did needle-sharing among narcotics addicts.

By those tokens, men and women who engaged in heterosexual,vaginal intercourse were observing "safe sex." That scenario stillseems to make sense, up to a point, in the First World of WesternEurope and North America, but not in Africa and Asia. On those twoThird World continents, 90 percent of HIV infections arise fromheterosexual sex.

By contrast, only 10 percent of HIV-1-positive Americans, 5,000 to10,000 a year, contract their infection heterosexually. This statisticmay change somewhat for the worse, warns Max Essex, chairman ofthe Harvard University AIDS Institute, in Cambridge, Mass.

Heterosexual HIV infection derives from two converging factors, onecellular, the other viral:

* Langerhans cells (no kin to the insulin-secreting Islets ofLangerhans) hang out in the epidermis _ the skin's outer layer. Thejob of these leukocytes is to capture invading antigens and bring themto the attention of the immune system's lymph nodes. Langerhanscells (LC) line the epithelial surfaces of the human reproductive tract.

* HIV-1E, the fifth of HIV-1's nine subtypes, binds more tightly tothose LCs than does HIV-1B, which predominates in the U.S. andWestern Europe These molecular variants, labeled alphabeticallyfrom A through H plus O, tend to segregate geographically.

Thus, HIV-1B has a virtual monopoly on the virus in the U.S. HIV-1E predominates in Thailand, where heterosexual infection is therule, not the exception _ contrary to the U.S. state of affairs.

Thai `E' Spreads Among Heterosexuals

Harvard's Essex, and his collaborators have confirmed that the Thai"E" subtype of HIV-1 spreads much more easily amongheterosexuals than the U.S. "B" subtype. "If HIV-1E takes hold herein the U.S., he said, "we could face a much more significant epidemicamong heterosexuals."

An article in today's Science documents the Harvard institute'ssurvey of HIV-1 variants worldwide, and their impact on infection.Its title: "HIV Langerhans' cell tropism [attraction] associated withheterosexual transmission of HIV."

Essex, the paper's senior author, told BioWorld Today: "The LCexperts say that those Langerhans cells are highly represented in suchtissues as vagina, cervix and foreskin, but not in the lining of therectum."

He added: "In our Science paper, we were testing whether or not theE virus, which is more associated with the heterosexual epidemic inAsia and Africa, grew better in these LC cells _ which are morerepresentative of the reproductive tract cells of entry _ than B virus,which is not associated with heterosexual epidemics, either in theU.S. or in those other places."

Together with Thai co-authors, the Harvard group compared thepreference of LCs for B vs. E virus in 15 B-infected Americans with18 E-positive Thai subjects. "We showed that E grows better in LCsthan B," Essex summed up. "In the U.S., B is certainly transmitted byheterosexual intercourse, but not as efficiently as those other virusesare elsewhere, even compared to B elsewhere."

Epidemiologically, 90 percent of Thailand's HIV-1E-positivepopulation are heterosexuals, compared with 10 percent of the HIV-1B positives in the U.S.

Now HIV-1E has made a landfall on the American continent. Essexrecalled a report in The Lancet late last year: "It was first detectedamong military personnel in San Diego, presumably returning fromassignment in Asia."

His team is now "trying to identify the LC receptor for HIV, lookingat other HIV-1 subtypes in other places, such as India, which issubtype C, and Japan, where Es have already arrived."

As for Haitians, Essex observed that "they are largely heterosexual,and probably have mainly the B subtype." He added, "I don't thinkanyone knows to this day if they got infected from the U.S. or viceversa."

Essex explained that the subtyping classification system "is based ona 25-to-30-percent difference in the HIV-1 envelope gene. This hasabout 520 amino acids, so the degree of difference between an A vs.a B, or a B vs. E, might be 150 or 160 residues."

"Only the first five subtypes, A through E," he observed, "areresponsible for the big epidemics. Since we now know that E and Cinfect Langerhans cells better than B, LCs are the likely route ofinfection by the heterosexual vaginal route. This is probably becausetheir receptor, which differs from the receptor on blood cells, hashigher affinity to HIV."

This has implications for AIDS vaccine development, Essex pointedout:. "Even if you wanted a vaccine to protect against heterosexualinfection, and you were only concerned about B _ which I don'tthink you have the luxury of doing any more _ the immunogenicsequences on the E or C envelope would probably be better than B toinduce immunity."

He went on: "As for how this might impact on biotech corporation Xor Y, in terms of long-range planning, it says that this is a constantlychanging epidemic. It's changed in ways that weren't even predictedtwo years ago.

"So it may indeed be more compelling," he concluded, "to make amulti-subtype vaccine, or a heterosexual subtype vaccine, to protectagainst the possibility that we will have a heterosexual epidemicexpanding before we realize it." n

-- David N. Leff Science Editor

(c) 1997 American Health Consultants. All rights reserved.