How human-like gene protects chimpanzees infected with AIDS
Drugs should be given at diagnosis not when condition worsens, landmark trial reveals
United States (US) scientists have found a gene for what’s known as the major histocompatibility complex (MHC)—cell surface molecules that help the immune system recognize foreigners—that was remarkably similar to one in humans that allows infected people to keep the virus in check for decades.
Prof. Peter Parham and his postdoctoral student, Emily Wroblewski, at Stanford University in Palo Alto, California, report in PLOS Biology that MHC seemed to be doing the same thing in SIVcpz-infected Gombe chimps.
SIVcpz, according to the study, is a retrovirus that is HIV’s predecessor.
According to Wikipedia, Simian immunodeficiency viruses (SIVs) are retroviruses able to infect at least 45 species of African non-human primates.
Wikipedia notes: “Based on analysis of strains found in four species of monkeys from Bioko Island, which was isolated from the mainland by rising sea levels about 11,000 years ago, it has been concluded that SIV has been present in monkeys and apes for at least 32,000 years, and probably much longer.
“Virus strains from two of these primate species, SIVsmm in sooty mangabeys and SIVcpz in chimpanzees, are believed to have crossed the species barrier into humans, resulting in HIV-2 and HIV-1, respectively. The most likely route of transmission of HIV-1 to humans involves contact with the blood of chimps that are often hunted for bushmeat in Africa.”
According to the study, Parham was skeptical when Wroblewski first showed him data suggesting a gene in some wild chimpanzees infected with the AIDS virus closely resembled one that protects humans from HIV.
Wroblewski had joined Parham’s microbiology and immunology group at Stanford University in Palo Alto, California, after doing behavioral studies of wild chimpanzees at Gombe Stream National Park in Tanzania. Her new genetic analysis studied a few hundred fecal samples collected from Gombe chimps, many of which were infected with SIVcpz.
Parham said: “I thought she might not know what she’s doing here. The MHC genetics are notoriously difficult to study and that her fieldwork had focused on mating patterns. But I was wrong.”
As Wroblewski, Parham, and co-authors explain in a PLOS Biology study published online Tuesday, they analyzed stool samples dating back 15 years and sequenced immune system genes from 125 chimpanzees. The animals live in three separate but overlapping communities: Two have a SIVcpz prevalence of about 12 per cent, whereas the third, in the southern portion of the park, has a prevalence of 46.1 per cent. SIVcpz-infected chimps have a significantly higher frequency of the relatively rare genetic variant that is linked to protection from disease in humans.
Meanwhile, experts have halted a major global trial 18 months early after ‘clear-cut proof’ that immediate treatment improves patients’ chances.
They advise that rather than wait until a person’s immune system is weakened by the virus, it is important to begin antiretroviral therapy straight away.
Scientists have hailed the findings groundbreaking, noting they mark the first time a major clinical randomised trial has provided evidence in support of treating all HIV positive individuals, regardless of the progression of their infection.
For many patients, the drugs are only prescribed when their CD4+ cell count – a key measure of how strong the immune system is – falls below a certain level.
A new study by scientists in 35 countries found antiretroviral drugs should be given to all HIV positive patients regardless of how advanced their infection is. The START trial, led by a team at the University of Minnesota, was halted 18 months early after the findings were described as ‘clear-cut proof’
The fall indicates the body’s immune system is weakened and is therefore more vulnerable to the effects of HIV.
In Nigeria, the National Agency for the Control of AIDS (NACA) guideline stipulates that treatment should be initiated when the CD4 count, a marker for the immune system, is 300 and below.
In the United Kingdom (UK), the National Health Service (NHS) guidelines dictate people who are HIV positive undergo regular blood tests to monitor the progress of the infection before embarking on treatment.
It involves monitoring the amount of virus in the blood – the viral load – and the effect HIV is having on the immune system.
This is determined by measuring CD4+ levels – the lymphocyte cells in the blood that are vital for fighting infections.
Treatment is usually recommended once CD4+ levels have fallen towards or below 350, regardless of whether a person is showing signs of HIV.
In the United States (US), the Centers for Disease Control and Prevention already recommends starting treatment immediately after diagnosis.
An evolutionary biologist at the University of California, San Diego Pascal Gagneux, who has done both genetic analyses of chimpanzees and behavioral studies of wild communities, said: “It possibly puts a finger on natural selection in the act. When humans and chimps were part of the same population, there may have been a retrovirus that used a couple of tricks still effective against HIV and SIVcpz today. This super-old genetic variant may be shared between humans and chimps because the pathogens can’t adapt to it.”
It has been shown that chimpanzees and humans had a common ancestor some six million years ago.
In humans, the protective MHC gene, known as HLA-B*57:01, has acquired a level of fame in HIV research. The gene is found at a higher frequency in humans known as “elite controllers,” who for many years keep the virus at very low levels without taking antiretroviral drugs.
Studies have shown that the gene works by revving up production of killer cells that directly target and eliminate cells infected with HIV. In essence, HLA-B*57:01 codes for a protein on cell surfaces that hoists up little pieces of the virus, which, in turn, tell immune killer cells that this is an enemy that should be destroyed.
The chimpanzee gene, dubbed Patr-B_06:03, is not identical to HLA-B*57:01, but is closely aligned on a genetic tree. Wroblewski and co-workers analyzed the levels of SIVcpz in infected chimps that had this
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