AIDS papers
From Augix' Wiki
Center Puts Hold on Mangabey Experiments
AIDS researchers study sooty mangabeys because SIV, HIV's cousin, naturally infects these African monkeys but rarely causes harm
Sooty mangabeys have high levels of SIV in their blood but show no immune damage, mangabeys remain unharmed by SIV because, unlike humans, they do not "overactivate" their immune systems when confronted with the virus.
HIV discovery in primates points way for AIDS research
Scientists say they have discovered why some monkeys are resistant to infection with the AIDS virus.
Normally, a virus spreads through the body by entering cells, hijacking their machinery, and using it to make new copies of itself. But monkeys have a protein called TRIM5-alpha that is somehow able to stop the virus from shedding its protective coat after it enters a healthy cell. The shedding of the coating is poorly understood but considered essential to the infection cycle.
HIV's ancient legacy
Lentiviruses may have vexed nonhuman primates for millions of years.
There were primate lentiviral epidemics five to ten million years ago The convergent evolution of TRIMCyp demonstrates the importance of retroviral defences during primate evolution, says Nathan Wolfe, an infectious disease researcher at the University of California, Los Angeles. “When you see evidence of convergent evolution in nature, it’s generally the sign of a pretty powerful selective force,” he says. “This really emphasizes how important retroviruses are to the evolution of nonhuman primates.”
Origins of HIV and the Evolution of Resistance to AIDS
Naturally infected nonhuman primates are relatively resistant to AIDS-like disease, Further understanding of host resistance factors and the mechanisms of disease in natural primate hosts may provide insight into unexplored therapeutic avenues for the prevention of AIDS
Retroviruses and primate evolution
Human endogenous retroviruses (HERVs), probably representing footprints of ancient germ-cell retroviral infections, occupy about 1% of the human genome. Comparative analysis of HERVs, HERV LTRs, neighboring genes, and their regulatory interplay in the human and ape genomes will help us to understand the possible impact of HERVs on evolution and genome regulation in the primates.
The Chimp Genome Reveals A Retroviral Invasion In Primate Evolution
retroelements: genomic elements that are transcribed into RNA, reverse-transcribed into DNA, and then reinserted into a new spot in the genome
In a new study, Evan Eichler and colleagues scanned finished chimpanzee genome sequence for endogenous retroviral elements, and found one (called PTERV1) that does not occur in humans. Searching the genomes of a subset of apes and monkeys revealed that the retrovirus had integrated into the germline of African great apes and Old World monkeys—but did not infect humans and Asian apes (orangutan, siamang, and gibbon). This undermines the notion that an ancient infection invaded an ancestral primate lineage, since great apes (including humans) share a common ancestor with Old World monkeys.
The Evolution Of The Monkey Gene That Blocks AIDS
According to evolutionary biologists, different species' acquisition of a similar adaptation is called "convergent evolution." One example of this is how birds and bats independently developed flight. The Harvard team remarks that an unequivocal and striking example of convergent evolution is seen in the genetic evidence of the two TRIM5-CypA genes. Researchers believe that it is rare for these kinds of molecular events to occur that are required to construct the two TRIM5-CypA genes.
The origin of AIDS and HIV and the first cases of AIDS
there is now clear evidence to prove that HIV causes AIDS. So, in order to find the source of AIDS, it is necessary to look for the origin of HIV, and find out How, When and Where HIV first began to cause disease in humans. HIV is a lentivirus, and like all viruses of this type, it attacks the immune system. Lentiviruses are in turn part of a larger group of viruses known as retroviruses. The name 'lentivirus' literally means 'slow virus' because they take such a long time to produce any adverse effects in the body. They have been found in a number of different animals, including cats, sheep, horses and cattle. However, the most interesting lentivirus in terms of the investigation into the origins of HIV is the Simian Immunodeficiency Virus (SIV) that affects monkeys. It is now generally accepted that HIV is a descendant of a Simian Immunodeficiency Virus because certain strains of SIVs bear a very close resemblance to HIV-1 and HIV-2, the two types of HIV.
Understanding Primate Evolution Could Aid HIV Research
TRIM5 allows most primates to inhibit the human immunodeficiency virus and other retroviruses, which use reverse transcription to insert themselves into their host’s genome. It turns out that TRIM5 exists in all primates, humans included, and that it’s involved in a rapid evolutionary back and forth with retroviruses: Each species has a unique TRIM5 gene that has evolved to deflect retroviruses, and each retrovirus has mutated in different ways to evade it in its particular host.
One change in particular, the insertion of a protein called cyclophilin into the owl monkey’s TRIM5 gene to create a hybrid TRIMcyp protein, has proven surprisingly potent at blocking HIV. Now, a study published online by the Proceedings of the National Academy of Sciences shows that in the pigtail macaque, the same protein inserted in nearly the same place had the opposite result — pigtail monkeys are curiously vulnerable to the virus.
Surprised that one species of macaque could be so different from another in its ability to resist HIV.
What surprised the researchers even more is that TRIMcyp is present in monkey species that evolved on different continents. Pigtail macaques live primarily in Southeast Asia, owl monkeys only in Central and South America. “This indicates that an intuitively unlikely evolutionary event occurred not only once but twice, in two primate species separated by 35 or so million years of evolution.
Why Old World Monkeys Are Resistant to HIV-1
Humans have been exposed to retroviruses for millions of years. Indeed, a significant portion of our genome consists of endogenous retroviruses--reminders of our vulnerability to past infections. The HIV/AIDS epidemic, which began nearly a century ago when simian immunodeficiency virus (SIV) passed from chimpanzees into a human host, is the latest episode in the longstanding coevolutionary struggle between retroviruses and their hosts.
Human immunodeficiency virus type 1 (HIV-1) causes AIDS in humans, and to a lesser extent, in chimpanzees (1, 2). However, not long after the discovery of HIV-1, scientists realized that certain primate species were resistant to HIV-1 infection. In particular, monkeys from Africa and Asia, referred to as Old World monkeys, could not be infected with HIV-1 and did not develop AIDS (3). This discovery brought both excitement and frustration. The block to HIV-1 replication in Old World monkey cells hindered efforts to develop an animal model for testing drugs and vaccines. On the other hand, Old World monkeys had evolved for millions of years in Africa--the epicenter of the current HIV-1 epidemic. Perhaps exposure to past HIV-1-like epidemics led to the emergence of an antiviral defense that protected them against HIV-1.
Using a genetic screen, we identified TRIM5 as the primary block to HIV-1 replication in Old World monkey cells (5). The expression of rhesus monkey TRIM5 in human cells potently inhibited HIV-1 infection and prevented the accumulation of reverse transcripts. Importantly, reducing the expression of TRIM5 in rhesus monkey cells with small interfering RNA relieved the block to HIV-1.
The discovery of TRIM5 not only answered a long-standing question in the HIV field, it also revealed a new pathway that protects cells from retroviral infection. The human genome encodes more than 50 members of the TRIM family. Recently, TRIM25 was shown to be essential for RIG-I-mediated antiviral activity (15) and TRIM family members such as TRIM1, TRIM19 (PML), and TRIM22, may block other viruses (16).
At a time when policy-makers and the public express frustration over our inability to produce an HIV vaccine, it is hoped that the discovery of TRIM5 will precipitate new ideas for how to protect human hosts from retroviral infection. Perhaps in the case of retroviruses, innate intracellular immunity mediated by factors like TRIM5 and APOBEC play a particularly crucial role. Efforts aimed at enhancing these innate immune defenses may ultimately prove to be more effective at protecting humans from HIV than vaccine strategies aimed primarily at stimulating humoral or cellular immune responses.
