The University of Nebraska-Lincoln reports evidence that supports the theory of the origins of HIV, and in particular, confirms that forms of HIV can cross species from chimps to humans.

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SIV strains, which have not previously been found in humans, have the potential to cause another HIV-like infection.

HIV attacks the immune system by destroying cells that fight disease and infection. There is no cure for HIV, but with medical care and treatments, most people with the virus can live a long and productive life.

More than 1.2 million people in the United States are estimated to have HIV, and 1 in 8 are unaware that they have the virus.

The origin of HIV has been the cause of much debate among scientists. The most commonly accepted theory identifies a type of chimpanzee in Central or West Africa as the source of HIV infection in humans.

Scientists suggest that the chimpanzee form of the immunodeficiency virus, called simian immunodeficiency virus (SIV), was potentially transmitted to humans and mutated into HIV.

The transmission from chimpanzees to humans was thought to occur when humans hunted chimps for meat in the early 1900s and came into contact with their blood.

In previous research, some scientists discovered a strain of SIV in a chimpanzee that was almost identical to HIV in humans, which validated the view that chimps were the source of HIV-1 and, furthermore, that the virus had crossed species.

The new study, led by senior author Qingsheng Li, associate professor of biological sciences and member of the Nebraska Center for Virology, supports the hypothesis of HIV originating from SIV.

The research team reports the first in-vivo evidence that strains of chimpanzee-carried SIVs can infect human cells. The strains involved are ancestors of HIV-1 M - the strain of HIV responsible for the global HIV pandemic - and another strain found in Cameroon.

Non-human-related SIV strains replicate at a very high level

After human cells were repeatedly exposed to SIV ancestors of HIV strains not seen in humans, Li and colleagues observed that the strains invaded the human cells.

Li says: "The question was whether SIV strains that have not been found in humans have the potential to cause another HIV-like infection. The answer is that, actually, they do. They get replicated at a very high level. It's surprising."

To conduct the experiment, the researchers implanted human tissues and stem cells into mice to mirror the human immune system. They aimed to evaluate why certain strains of immunodeficiency virus have transferred to humans, while others have not.

The mice were divided into groups and injected with small doses of four SIV strains.

The SIV ancestors of HIV-1 and the Cameroon strains infected the mice more efficiently and with fewer attempts than the other two SIV strains not observed in humans.

Li explains that the difference in the results between the SIV strains could be because the pandemic-causing HIV-1 M shares more genes with the Cameroon strain than the other two strains.

He says that based on the experiments, there are clear differences between the strains, which implies that there might be differences in the chance of cross-species transmission when an individual is subjected to one strain versus another.

Experimental approach may prove vital in identifying zoonotic viruses

Another significant outcome was evidence to support the idea that the SIV strains mutate after entering human cells to weaken human-specific blockades against infection. The team noted that within a 14-week period, the same viral gene in two SIV strains experienced mutations in two positions.

"The emergence and re-emergence of infectious diseases has become a constant threat to global health, social stability, safety and economic systems. Bill Gates recently said that nuclear war is no longer the (biggest) threat to our safety; emerging infectious diseases are. That's probably true."

Qingsheng Li

Li and lead author Zhe Yuan, a doctoral student in biological sciences, highlight the importance of being proactive with identifying viruses that can transmit from animals to human, using the recent outbreak of the Zika virus as an example.

Yuan says that given the dynamic nature of HIV and zoonotic diseases to cause epidemics and pandemics, the approach taken for this study could assess the potential threat from other SIVs and animal-carried viruses.

"I think this analysis of the disease is very important for public health. We want to explore this platform for evaluating new, emerging infectious diseases," concludes Yuan.

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