This TL definitely isn't or shouldn't be dead. Because it has set loose a major butterfly.
HIV first spread from either a bonobo or a gorilla to a human in the late 19th or early 20th Century in Cameroon or French Congo in both TLs. As this excerpt from the Wikipedia article on History of AIDS transmission illustrates OTTL, transmission of HIV was both encouraged by the conditions of colonialism and slowed by the remoteness of Cameroon and French Congo ITT, with the first Western deathsf from AIDS in 1959 and the 1960s. Because of massive Western migration to Central Africa, ITTL, the transmission of AIDS will be a lot faster. But knowledge of viruses and immunity will be a lot less. And in Europe in the 1940s, there is a lot of antisemitism. And circumcision provides resistance to AIDS in males. Ouch!
[edit] HIV-1 from chimpanzees and gorillas to humans
Scientists generally accept that the known strains (or groups) of
HIV-1 are most closely related to the simian immunodeficiency viruses (SIVs) endemic in wild
ape populations of West Central African forests. Particularly, each of the known HIV-1 strains is either closely related to the
SIV that infects the
chimpanzee subspecies
Pan troglodytes troglodytes (SIVcpz), or to the SIV that infects
Western lowland gorillas (
Gorilla gorilla gorilla), called SIVgor.
[3][4][5][6][7][8] The pandemic HIV-1 strain (group M or Main) and a very rare strain only found in a few Cameroonian people (group N) are clearly derived from SIVcpz strains endemic in
Pan troglodytes troglodytes chimpanzee populations living in
Cameroon.
[3] Another very rare HIV-1 strain (group P) is clearly derived from SIVgor strains of Cameroon.
[6] Finally, the primate ancestor of HIV-1 group O, a strain infecting tens of thousands of people mostly from Cameroon but also from neighboring countries, is still uncertain, but there is evidence that it is either SIVcpz or SIVgor.
[5] The pandemic HIV-1 group M is most closely related to the SIVcpz collected from the southeastern rain forests of Cameroon (modern
East Province) near the
Sangha River.
[3] Thus, this region is presumably where the virus was first transmitted from chimpanzees to humans. However, reviews of the epidemiological evidence of early HIV-1 infection in stored blood samples, and of old cases of AIDS in Central Africa have led many scientists to believe that HIV-1 group M early human center was probably not in Cameroon, but rather farther south in the
Democratic Republic of the Congo, more probably in its capital city,
Kinshasa.
[3][9][10][11]
Using
HIV-1 sequences preserved in human biological samples along with estimates of viral mutation rates, scientists calculate that the jump from chimpanzee to human probably happened during the late 19th or early 20th century, a time of rapid urbanisation and colonisation in equatorial Africa. Exactly when the
zoonosis occurred is not known. Some molecular dating studies suggest that HIV-1 group M had its
most recent common ancestor (MRCA) (that is, started to spread in the human population) in the early 20th century, probably between 1915 and 1941.
[12][13][14] A study published in 2008, analyzing viral sequences recovered from a recently discovered biopsy made in
Kinshasa, in 1960, along with previously known sequences, suggested a common ancestor between 1873 and 1933 (with central estimates varying between 1902 and 1921).
[15][16]
Genetic recombination had earlier been thought to "seriously confound" such phylogenetic analysis, but later "work has suggested that recombination is not likely to systematically bias [results]", although recombination is "expected to increase variance".
[15] The results of a 2008 phylogenetics study support the later work and indicate that HIV evolves "fairly reliably".
[15][17]
[edit] HIV-2 from sooty mangabeys to humans
Similar research has been undertaken with
SIV strains collected from several wild
sooty mangabey (
Cercocebus atys atys) (SIVsmm) communities of the West African nations of
Sierra Leone, Liberia, and
Ivory Coast. The resulting phylogenetic analyses show that the viruses most closely related to the two strains of
HIV-2 which spread considerably in humans (HIV-2 groups A and B) are the SIVsmm found in the sooty mangabeys of the Tai forest, in western
Ivory Coast.
[2]
There are six additional known
HIV-2 groups, each having been found in just one person. They all seem to derive from independent transmissions from
sooty mangabeys to humans. Groups C and D have been found in two people from
Liberia, groups E and F have been discovered in two people from
Sierra Leone, and groups G and H have been detected in two people from the
Ivory Coast. These
HIV-2 strains are probably
dead-end infections, and each of them is most closely related to SIVsmm strains from
sooty mangabeys living in the same country where the human infection was found.
[2][11][18]
Molecular dating studies suggest that both the epidemic groups (A and B) started to spread among humans between 1905 and 1961 (with the central estimates varying between 1932 and 1945).
[19] [20]
See also this article about
HIV types, groups, and subtypes.
[edit] Bushmeat practice
According to the
natural transfer theory (also called 'Hunter Theory' or 'Bushmeat Theory'), the "simplest and most plausible explanation for the cross-species transmission"
[7] of SIV or HIV (post mutation), the virus was transmitted from an
ape or
monkey to a human when a hunter or
bushmeat vendor/handler was bitten or cut while hunting or butchering the animal. The resulting exposure to blood or other bodily fluids of the animal can result in SIV infection.
[21] A recent serological survey showed that human infections by
SIV are not rare in Central Africa: the percentage of people showing seroreactivity to
antigens — evidence of current or past SIV infection — was 2.3% among the general population of
Cameroon, 7.8% in villages where bushmeat is hunted or used, and 17.1% in the most exposed people of these villages.
[22] How the SIV virus would have transformed into HIV after infection of the hunter or
bushmeat handler from the ape/monkey is still a matter of debate, although natural selection would favor any viruses capable of adjusting so that they could infect and reproduce in the T cells of a human host.
[edit] Emergence
[edit] Conditions for successful zoonosis
Zoonosis (transfer of a
pathogen from non-human animals to humans) and subsequent spread of the pathogen between humans, requires the following conditions:
- a human population;
- a nearby population of a host animal;
- an infectious pathogen in the host animal that can spread from animal to human;
- interaction between the species to transmit enough of the pathogen to humans to establish a human foothold, which could have taken millions of individual exposures;
- ability of the pathogen to spread from human to human (perhaps acquired by mutation);
- some process allowing the pathogen to disperse widely, preventing the infection from "burning out" by either killing off its human hosts or provoking immunity in a local population of humans.
[edit] The unresolved issues about HIV origins and emergence
It is clear that the several HIV-1 and HIV-2 strains descend from SIVcpz, SIVgor, and SIVsmm viruses,
[2][5][6][7][9][18] and that bushmeat practice provides the most plausible venue for cross-species transfer to humans.
[7][9][22] However, some loose ends remain unresolved.
It is not yet explained why only four HIV groups (
HIV-1 groups M and O, and
HIV-2 groups A and B) spread considerably in human populations, despite
bushmeat practices being very widespread in Central and West Africa,
[10] and the resulting human
SIV infections being common.
[22]
It remains also unexplained why all epidemic HIV groups emerged in humans nearly simultaneously, and only in the 20th century, despite very old human exposure to SIV (a recent phylogenetic study demonstrated that SIV is at least tens of thousands of years old).
[23]
The discovery of the main HIV / SIV phylogenetic relationships permits explaining
broadly HIV
biogeography: the early centers of the
HIV-1 groups were in Central Africa, where the primate reservoirs of the related SIVcpz and SIVgor viruses (
chimpanzees and
gorillas) exist; similarly, the
HIV-2 groups had their centers in West Africa, where
sooty mangabeys, which harbor the related SIVsmm virus, exist. However these relationships do not explain more detailed patterns of biogeography, such as why epidemic HIV-2 groups (A and B) only evolved in the
Ivory Coast, which is only one of six countries harboring the
sooty mangabey. It is also unclear why the SIVcpz endemic in the
chimpanzee subspecies
Pan troglodytes schweinfurthii (inhabiting the
Democratic Republic of Congo, Central African Republic,
Rwanda, Burundi,
Uganda, and
Tanzania) did not spawn an epidemic HIV-1 strain to humans, while the
Democratic Republic of Congo was the main center of HIV-1 group M, a virus descended from SIVcpz strains of a subspecies (
Pan troglodytes troglodytes) that does not exist in this country.
[edit] Theories of HIV origin and epidemic emergence
Several of the theories of HIV origin put forward (described below) attempt to explain the unresolved loose ends described in the previous section. Most of them accept the (above described) established knowledge of the HIV/SIV phylogenetic relationships, and also accept that
bushmeat practice was the most likely cause of the initial transfer to humans. All of them propose that the simultaneous epidemic emergences of four HIV groups in the late 19th-early 20th century, and the lack of previous emergences, are explained by new factor(s) that appeared in the relevant African regions in that timeframe. These new factor(s) would have acted either to increase human exposures to SIV, to help it to adapt to the human organism by
mutation (thus enhancing its between-humans transmissibility), or to cause an initial burst of transmissions crossing an
epidemiological threshold, and therefore increasing the odds of continued spread.
[edit] Social changes and urbanization
It was proposed by Beatrice Hahn, Paul Sharp, and colleagues that "[the epidemic emergence of HIV] most likely reflects changes in population structure and behaviour in Africa during the 20th century and perhaps medical interventions that provided the opportunity for rapid human-to-human spread of the virus".
[7] After the
Scramble for Africa started in the 1880s, European colonial powers established cities, towns, and other colonial stations. A largely masculine labor force was hastily recruited to work in fluvial and sea ports, railways, other infrastructures, and in plantations. This disrupted traditional tribal values, and favored
sexual promiscuity. In the nascent cities women felt relatively liberated from rural tribal rules
[24] and many remained unmarried or divorced during long periods,
[10][25] this being very rare in African traditional societies.
[26] This was accompanied by unprecedented increase in people's movements.
Michael Worobey and colleagues observed that the growth of cities had probably a role in the epidemic emergence of HIV, since the phylogenetic datations of the two older strains of
HIV-1 (groups M and O), suggest that these viruses started to spread soon after the main Central African colonial cities were founded.
[15]
[edit] Heart of Darkness
Amit Chitnis, Diana Rawls, and Jim Moore proposed that HIV may have emerged epidemically as a result of the harsh conditions, forced labor, displacement, and unsafe injection and
vaccination practices associated with
colonialism, particularly in
French Equatorial Africa.
[27] The workers in plantations, construction projects, and other colonial enterprises were supplied with
bushmeat, this contributing to increase this activity, and then exposures to SIV. Several historical sources support the view that
bushmeat hunting indeed increased, both because of the necessity to supply workers and because firearms became more widely available.
[27][28][29]
The colonial authorities also gave many
vaccinations against
smallpox, and injections, of which many would be made without sterilising the equipment between uses (unsafe or unsterile injections). Chitnis
et al. proposed that both these
parenteral risks and the prostitution associated with forced labor camps could have caused serial transmission (or
serial passage) of SIV between humans (see discussion of this in the next section).
[27] In addition, they proposed that the conditions of extreme stress associated with forced labor could depress the
immune system of workers, therefore prolonging the primary
acute infection period of someone newly infected by SIV, thus increasing the odds of both adaptation of the virus to humans, and of further transmissions.
[30]
The authors predicted that HIV-1 originated in the area of
French Equatorial Africa, and in the early 20th century (when the colonial abuses and forced labor were at their peak). Later researches proved these predictions mostly correct: HIV-1 groups M and O started to spread in humans in late 19th–early 20th century.
[12][13][14][15] And all groups of HIV-1 descend from either SIVcpz or SIVgor from
apes living to the west of the
Ubangi River, either in countries which belonged to the
French Equatorial Africa federation of colonies, in
Equatorial Guinea (then a Spanish colony), or in
Cameroon (which was a German colony between 1884 and 1916, then fell to Allied forces in World War I, and had most of its area administered by France, in close association with
French Equatorial Africa).
This theory was later dubbed 'Heart of Darkness' by Jim Moore,
[31] alluding to
the book of the same title written by
Joseph Conrad, the main focus of which is colonial abuses in equatorial Africa.
[edit] Unsterile injections
In several articles published since 2001, Preston Marx, Philip Alcabes, and Ernest Drucker proposed that HIV emerged because of rapid serial human-to-human transmission of
SIV (after a
bushmeat hunter or handler became SIV-infected) through unsafe or unsterile injections.
[16][18][32][33] Although both Chitnis
et al.[27] and Sharp
et al.[7] also suggested that this may have been one of the major risk factors at play in HIV emergence (see above), Marx
et al. enunciated the underlying mechanisms in greater detail, and wrote the first review of the injection campaigns made in colonial Africa.
[18][32]
Central to Marx
et al. argument is the concept of adaptation by
serial passage (or serial transmission): an adventitious virus (or other
pathogen) can increase its biological
adaptation to a new host species if it is rapidly transmitted between hosts, while each host is still in the
acute infection period. This process favors the accumulation of
adaptive mutations more rapidly, therefore increasing the odds that a better adapted viral variant will appear in the host before the
immune system suppresses the virus.
[18] Such better adapted variant could then survive in the human host for longer than the short
acute infection period, in high numbers (high
viral load), which would grant it more possibilities of epidemic spread.
Marx
et al. reported experiments of cross-species transfer of SIV in captive monkeys (some of which made by themselves), in which the use of
serial passage helped to adapt SIV to the new monkey species after passage by three or four animals.
[18]
In agreement with this model is also the fact that, while both
HIV-1 and
HIV-2 attain substantial
viral loads in the human organism, adventitious
SIV infecting humans seldom does so: people with SIV antibodies often have very low or even undetectable SIV
viral load.
[22] This suggests that both
HIV-1 and
HIV-2 are adapted to humans, and
serial passage could have been the process responsible for it.
Marx
et al. proposed that unsterile injections (that is, injections where the needle or syringe is reused without sterilization or cleaning between uses), which were likely very prevalent in Africa, during both the colonial period and afterwards, provided the mechanism of
serial passage that permitted HIV to adapt to humans, therefore explaining why it emerged epidemically only in the 20th century.
[18][32]
[edit] Massive injections of the antibiotic era
Marx
et al. emphasize the massive number of injections administered in Africa after
antibiotics were introduced (around 1950) as being the most likely implicated in the origin of HIV because, by these times (roughly in the period 1950 to 1970), injection intensity in Africa was maximal. They argued that a
serial passage chain of 3 or 4 transmissions between humans is an unlikely event (the probability of transmission after a needle reuse is something between 0.3% and 2%, and only a few people have an acute SIV infection at any time), and so HIV emergence may have required the very high frequency of injections of the
antibiotic era.
[18]
The molecular dating studies place the initial spread of the epidemic HIV groups before that time (see above).
[12][13][14][15][19][20] According to Marx
et al., these studies could have overestimated the age of the HIV groups, because they depend on a
molecular clock assumption, may not have accounted for the effects of
natural selection in the viruses, and the
serial passage process alone would be associated with strong
natural selection.
[18]
[edit] The injection campaigns against sleeping sickness
David Gisselquist proposed that the mass injection campaigns to treat
trypanosomiasis (
sleeping sickness) in Central Africa were responsible for the emergence of HIV-1.
[34] Unlike Marx
et al.,
[18] Gisselquist argued that the millions of unsafe injections administered during these campaigns were sufficient to spread rare HIV infections into an epidemic, and that evolution of HIV through
serial passage was not essential to the emergence of the HIV epidemic in the 20th century.
[34]
This theory focuses on injection campaigns that peaked in the period 1910–40, that is, around the time the
HIV-1 groups started to spread.
[12][13][14][15] It also focuses on the fact that many of the injections in these campaigns were intravenous (which are more likely to transmit SIV/HIV than subcutaneous or intramuscular injections), and many of the patients received many (often more than 10) injections per year, therefore increasing the odds of SIV
serial passage.
[34]
[edit] Other early injection campaigns
Jacques Pépin and Annie-Claude Labbé reviewed the colonial health reports of
Cameroon and
French Equatorial Africa for the period 1921–59, calculating the incidences of the diseases requiring intravenous injections. They concluded that
trypanosomiasis,
leprosy,
yaws, and
syphilis were responsible for most intravenous injections.
Schistosomiasis,
tuberculosis, and vaccinations against
smallpox represented lower
parenteral risks: schistosomiasis cases were relatively few; tuberculosis patients only became numerous after mid century; and there were few smallpox vaccinations in the lifetime of each person.
[35]
The authors suggested that the very high prevalence of the
Hepatitis C virus in southern
Cameroon and forested areas of
French Equatorial Africa(around 40–50%) can be better explained by the unsterile injections used to treat
yaws, because this disease was much more prevalent than
syphilis,
trypanosomiasis, and
leprosy in these areas. They suggested that all these parenteral risks caused, not only the massive spread of
Hepatitis C, but also the spread of other
pathogens, and the emergence of
HIV-1: "the same procedures could have exponentially amplified HIV-1, from a single hunter/cook occupationally infected with SIVcpz to several thousand patients treated with arsenicals or other drugs, a threshold beyond which sexual transmission could prosper."
[35] They do not suggest specifically
serial passage as the mechanism of adaptation.
According to Pépin's 2011 book,
The Origins of AIDS,
[36] the virus can be traced to a central African bush hunter in 1921, with colonial medical campaigns using improperly sterilized syringe and needles playing a key role in enabling a future epidemic. Pépin concludes that AIDS spread silently in Africa for decades, fueled by urbanization and prostitution since the initial cross-species infection. Pépin also claims that the virus was brought to the Americas by a Haitian teacher returning home from Zaire in the 1960s.
[37] Sex tourism and contaminated blood transfusion centers ultimately propelled AIDS to public’s consciousness in the 80s and a worldwide pandemic.
[36]
[edit] Genital ulcer diseases and sexual promiscuity
João Dinis de Sousa, Viktor Müller, Philippe Lemey, and Anne-Mieke Vandamme proposed that HIV became epidemic through sexual serial transmission, in nascent colonial cities, helped by a high frequency of
genital ulcers, caused by
genital ulcer diseases (GUD).
[10] GUD are simply
sexually transmitted diseases that cause genital ulcers; examples are
syphilis,
chancroid,
lymphogranuloma venereum, and
genital herpes. These diseases increase the probability of HIV transmission dramatically, from around 0.01–0.1% to 4–43% per heterosexual act, because the genital ulcers provide a portal of viral entry, and contain many activated
T cells expressing the
CCR5 co-receptor, the main cell targets of HIV.
[10][38]
[edit] The probable time interval of cross-species transfer
Sousa
et al. use molecular dating techniques to estimate the time when each HIV group split from its closest
SIV lineage. Each HIV group necessarily crossed to humans between this time and the time when it started to spread (the time of the
MRCA), because after the MRCA certainly all lineages were already in humans, and before the split with the closest
simian strain, the lineage was in a simian. HIV-1 groups M and O, split from their closest SIVs around 1876 (1847–1907), 1741 (1606–1870), respectively. HIV-2 did so around 1889 (1856–1922). This information, together with the datations of the HIV groups'
MRCAs (described above) mean that all HIV groups likely crossed to humans in late 19th—early 20th century.
[10]
[edit] Strong GUD incidence in nascent colonial cities
The authors reviewed colonial medical articles and archived medical reports of the countries at or near the ranges of
chimpanzees,
gorillas and
sooty mangabeys, and found that
genital ulcer diseases peaked in the colonial cities during their early growth period (up to 1935). The colonial authorities recruited men to work in railways, fluvial and sea ports, and other infrastructure projects, and most of these men did not bring their wives with them. Then, the highly male-biased
sex ratio favoured prostitution, which in its turn caused an explosion of
GUD (especially
syphilis and
chancroid). After the mid-1930s, people's movements were more tightly controlled, and mass surveys and treatments (of
arsenicals and other drugs) were organized, and so the GUD incidences started to decline. They declined even further after World War II, because of the heavy use of
antibiotics, so that, by the late 1950s,
Kinshasa (which is the probable center of HIV-1 group M) had a very low GUD incidence. Similar processes happened in the cities of
Cameroon and
Ivory Coast, where HIV-1 group O and HIV-2 respectively evolved.
[10]
Therefore, the peak GUD incidences in cities
[10] have a good temporal coincidence with the period when all main HIV groups crossed to humans and started to spread.
[10][12][13][14][15][19][20] In addition, the authors gathered evidence that
syphilis and the other GUDs were, like injections, absent from the densely forested areas of Central and West Africa before organized
colonialism socially disrupted these areas (starting in the 1880s).
[10] Thus, this theory also potentially explains why HIV emerged only after late 19th century.
[edit] Female circumcision
Uli Linke has argued that the practice of
female circumcision is responsible for the high incidence of AIDS in Africa, since intercourse with a circumcised female is conducive to exchange of blood.
[39]
[edit] Male circumcision distribution and HIV origins
Male
circumcision may reduce the probability of HIV acquisition by men (see article
Circumcision and HIV). Leaving aside blood
transfusions, the highest
HIV-1 transmissibility ever measured was from GUD-suffering female prostitutes to uncircumcised men—the measured risk was 43% in a single sexual act.
[38] Sousa
et al. reasoned that the adaptation and epidemic emergence of each HIV group may have required such extreme conditions, and thus reviewed the existing
ethnographic literature for patterns of male
circumcision and hunting of
apes and
monkeys for
bushmeat, focusing on the period 1880–1960, and on most of the 318
ethnic groups living in Central and West Africa.
[10] They also collected censuses and other literature showing the ethnic composition of colonial cities in this period. Then, they estimated the circumcision frequencies of the Central African cities over time.
Circumcision is nowadays almost universal in almost all countries of Central and West Africa. [
citation needed] However, Sousa
et al. charts reveal that male circumcision frequencies were much lower in several cities of these areas in early 20th century. The reason is that many
ethnic groups not performing circumcision by that time gradually adopted it, to imitate other ethnic groups and enhance the social acceptance of their boys (
colonialism produced massive intermixing between African ethnic groups).
[10][26] About 15–30% of men in
Kinshasa and
Douala in early 20th century should be uncircumcised, and these cities were the probable centers of HIV-1 groups M and O, respectively.
[10]
The authors studied early
circumcision frequencies in 12 cities of Central and West Africa, to test if this variable correlated with HIV emergence. This
correlation was strong for
HIV-2: among 6 West African cities that could have received immigrants infected with SIVsmm, the two cities from the
Ivory Coast studied (
Abidjan and
Bouaké) had much higher frequency of uncircumcised men (60–85%) than the others, and epidemic
HIV-2 groups emerged initially in this country only. This correlation was less clear for
HIV-1 in Central Africa.
[10]
[edit] Computer simulations of HIV emergence
Sousa
et al. then built
computer simulations to test if an 'ill-adapted SIV' (meaning a
simian immunodeficiency virus already infecting a human but incapable of transmission beyond the short
acute infection period) could spread in colonial cities. The simulations used
parameters of sexual transmission obtained from the current HIV literature. They modelled people's 'sexual links', with different levels of sexual partner change among different categories of people (prostitutes, single women with several partners a year, married women, and men), according to data obtained from modern studies of
sexual promiscuity in African cities. The simulations let the parameters (city size, proportion of people married,
GUD frequency, male
circumcision frequency, and transmission parameters) vary, and explored several scenarios. Each scenario was run 1,000 times, to test the probability of SIV generating long chains of sexual transmission. The authors postulated that such long chains of sexual transmission were necessary for the SIV strain to adapt better to humans, becoming a HIV capable of further epidemic emergence.
The main result was that
genital ulcer frequency was by far the most decisive factor. For the GUD levels prevailing in
Kinshasa, in early 20th century, long chains of SIV transmission had a high probability. For the lower
GUD levels existing in the same city in the late 1950s (see above), they were much less likely. And without GUD (a situation typical of villages in forested equatorial Africa before
colonialism) SIV could not spread at all. City size was not an important factor. The authors propose that these findings explain the temporal patterns of HIV emergence: no HIV emerging in tens of thousands of years of human slaughtering of
apes and
monkeys, several HIV groups emerging in the nascent, GUD-riddled, colonial cities, and no epidemically successful HIV group emerging in mid-20th century, when GUD was more controlled, and cities were much bigger.
Male
circumcision had little to moderate effect in their simulations, but given the geographical
correlation found, the authors propose that it could have had an indirect role, either by increasing
genital ulcer disease itself (it is known that
syphilis,
chancroid, and several other GUDs have higher incidences in uncircumcised men), or by permitting further spread of the HIV strain, after the first chains of sexual transmission permitted
adaptation to the human organism.
One of the main advantages of this theory is stressed by the authors: "It [the theory] also offers a conceptual simplicity because it proposes as causal factors for SIV adaptation to humans and initial spread the very same factors that most promote the continued spread of HIV nowadays: promiscuous sex, particularly involving sex workers, GUD, and possibly lack of circumcision."
[10]
[edit] Iatrogenic and other theories
Iatrogenic theories propose that medical interventions were responsible for HIV origins. By proposing factors that only appeared in Central and West Africa after the late 19th century, they seek to explain why all HIV groups also started after that.
The theories centered on the role of
parenteral risks, such as unsterile injections,
transfusions,
[18][27][34][35] or
smallpox vaccinations
[27] are accepted as plausible by most scientists of the field, and were already reviewed above.
[edit] Pathogenicity of SIV in non-human primates
In most non-human primate species, natural
SIV infection does not cause a fatal disease (but see below). Comparison of the gene sequence of SIV with HIV should therefore give us information about the factors necessary to cause disease in humans. The factors that determine the virulence of HIV as compared to most SIVs are only now being elucidated. Non-human SIVs contain a
nef gene that down-regulates
CD3,
CD4, and
MHC class I expression; most non-human SIVs therefore do not induce immunodeficiency; the
HIV-1 nef gene however has lost its ability to down-regulate CD3, which results in the immune activation and apoptosis that is characteristic of chronic HIV infection.
[40]
In addition, a long term survey of
chimpanzees naturally infected with SIVcpz in Gombe,
Tanzania, found that, contrary to the previous
paradigm, chimpanzees with SIVcpz infection do experience an increased mortality, and also suffer from a Human AIDS-like illness.
[41] SIV pathogenicity in wild animals could exist in other chimpanzee subspecies and other primate species as well, and stay unrecognized by lack of relevant long term studies.
[edit] History of spread
Main article:
Timeline of early AIDS cases
[edit] 1959: David Carr
David Carr was an apprentice printer (usually referred to, mistakenly, as a sailor; Carr had served in the Navy between 1955 and 1957) from Manchester, England who died in October 1959 following the failure of his immune system; he succumbed to pneumonia. Doctors, baffled by what he had died from, preserved 50 of his tissue samples for inspection. In 1990, the tissues were found to be HIV-positive. However, in 1992, a second test by AIDS researcher David Ho found that the strain of HIV present in the tissues was similar to those found in 1990 rather than an earlier strain (which would have mutated considerably over the course of 30 years). He concluded that the DNA samples provided actually came from a 1990 AIDS patient. Upon retesting David Carr's tissues, he found no sign of the virus.
[42]
[edit] 1959: Congolese man
One of the earliest documented HIV-1 infections was discovered in a preserved blood sample taken in 1959 from a man from Leopoldville, Belgian Congo (now
Kinshasa, Democratic Republic of the Congo).
[43] However, it is unknown whether this anonymous person ever developed AIDS and died of its complications.
[43]
[edit] 1960: Congolese woman
A second early documented HIV-1 infection was discovered in a preserved
lymph node biopsy sample taken in 1960 from a woman from Leopoldville, Belgian Congo.
[15]
[edit] 1969: Robert Rayford
Main article:
Robert Rayford
In May 1969 a 15-year-old African-American male named
Robert Rayford di