by Gertrud U. Rey
As discussed in my previous post, we first became aware of human immunodeficiency virus (HIV) in the early 1980s. However, when did the virus actually emerge in humans, and where did it come from?
There are two strains of HIV – HIV-1 and HIV-2. The vast majority of infections are caused by HIV-1, which is more common, more transmissible, and more pathogenic. HIV-1 is divided into four groups: M, N, O, and P. Of these, group M is the oldest and most widely-spread, and it is associated with the majority of global HIV disease. Soon after HIV-1 and HIV-2 were discovered, scientists learned that non-human primates in sub-Saharan Africa were infected with a variety of related viruses that were thereafter named simian immunodeficiency viruses (SIVs). The development of new and improved molecular epidemiology tools in the 1990s allowed experts to analyze nucleotide sequences from large numbers of HIV and SIV isolates, eventually leading to the conclusion that HIV-1 and HIV-2 must have resulted from separate spillovers of SIV from apes/monkeys to humans.
Viral DNA sequences extracted from blood and tissue samples collected from human and non-human animals in various geographic locations and at different time points can be compared. Using a calculation technique known as a molecular clock, researchers can then estimate the approximate time it took for sequences collected at later time points to diverge from ancestral sequences collected at earlier time points. The more similar two sequences are, the more likely they are to share a common ancestor, while greater differences suggest a more distant evolutionary relationship. To clarify, consider the following human analogy. Full siblings share about 50% of their DNA because they share a set of parents – ancestors from whom they are only removed by one generation. In contrast, cousins only share about 12.5% of their DNA because their ancestral origin goes back two generations to their shared set of grandparents. Using SIV samples obtained from non-human primates in Cameroon and applying molecular clock techniques that take into account the rate of evolution of HIV (also discussed in my previous post), scientists eventually deduced that HIV-1 group M evolved from an SIV-infected chimpanzee somewhere in the southeastern region of Cameroon during the first three decades of the 20th century.
This initial spillover from the chimpanzee to the first infected human most likely involved direct blood-to-blood contact, the most efficient means of transmission for SIV/HIV. A hypothetical scenario known as the “cut hunter theory” involves a hunter scouring the Cameroonian forest for bushmeat around 1920, a practice that was very common in that region at that time. This man caught a chimpanzee that unbeknownst to him was infected with SIV, and while dressing the carcass in preparation for later consumption, he accidentally cut and contaminated himself with the animal’s blood. During this interaction, SIV infected its new human host and became HIV, a random event known as “host switching.” The hunter then later passed the virus to his wife during sex. Both husband and wife likely transmitted the virus to other people in the area through shared syringe needles used by mobile clinic workers who routinely visited Cameroonian villages to treat people suffering from various tropical diseases. Treatment of these diseases was mandatory and involved repeated intravenous injections of drugs with glass syringes and needles that were re-used frequently without being sterilized. Newly infected people then traveled down the Sangha river, which connects southeastern Cameroon to Leopoldville, an important hub for trading and commerce, and the capital city of what was then the Belgian Congo (now Kinshasa in the Democratic Republic of Congo). This series of hypothetical events is consistent with the recovery of the oldest HIV-1 isolate extracted from the blood sample of a man who had died in Leopoldville/Kinshasa in 1959. Furthermore, the earliest strains of HIV-1 group M and all its subtypes were later identified in Leopoldville/Kinshasa, and many of these strains and subtypes remain restricted to that area until today. Taken together, these facts suggest that Leopoldville/Kinshasa was the epicenter for world-wide transmission of HIV-1.
The propagation of HIV-1 within Leopoldville/Kinshasa likely occurred through a combination of the growing local sex industry and clinics that specialized in treatment of tropical and sexually-transmitted diseases using intravenously injected drugs. Eventually the virus was exported to Haiti, likely through one or more of the numerous Haitian medical professionals who worked in the Congo around 1959/1960. A surge in gay sexual tourism in the 1970s further advanced its spread from Haiti to the US, eventually leading to its discovery in Los Angeles, San Francisco, and New York.
This story emphasizes the importance of a one health approach to disease prevention – a strategy that is cognizant of the interplay between human health and the health of animals in our shared environment. Knowing how viruses are transmitted and where they originate helps us stop future outbreaks at the source and may even prevent spillovers in the first place.
[Recommended readings: The Origins of AIDS by Jacques Pepin; Part VIII of Spillover by David Quammen; And the Band Played On by Randy Shilts. Please note that the reference to Gaëtan Dugas as “patient zero” in And the Band Played On is incorrect. Still, the book is a fascinating read.]