Monday, November 30, 2015


Of course, he didn't create it -- only found and defined it.
Humans are such sloppy thinkers!  Esp. when they are scared.

To write about HIV-AIDS is not the same as writing about the impact on human beings, whether gays or not.  Writing about HIV-AIDS is writing about a virus, which is what this disease (dis-ease) really is.  But a virus is so small that it’s a matter of molecules interacting, which is the way life functions as well as the map of what they should do.  Molecules, of course, are assembled from atoms in various ways and the arrangement and isotopes of atoms in the molecules make a difference -- things like “folding” and other mysterious bonds and reactions.  The virus itself is not human and will not respond to being stigmatized, punished, incarcerated, or denounced.  It can infect ANY human except for a very few who have a mutation, a gene that will prevent the virus from attaching.  

HIV-AIDS attacks the immune system that constantly sweeps the blood system to eliminate disease.  The result is a vulnerability disease, often killing because it prevents the body from healing itself.  One can die from something normally shrugged off.  It doesn't attack the fort, merely opens the gates to the hostiles.

A virus is the nucleus of a cell that has no cell, so goes seeking cells it can kidnap in order to reproduce.  It is a pirate virus that started as SIV [Simian Immunodeficiency Virus], then jumped to humans who hunted them.  HIV versions come in “strains” with slightly different genomes, some that are not pathogenic -- won’t make the victims sick.  Pygmies have antibodies for several of these immunodeficiency strains, probably because their hunting is arboreal: monkeys and apes.  HIV and SIV can kill gorillas and bonobos, but those strains have only affected local humans, mostly.  

One of the protections of remote communities that stay in one place is that there are few vectors in or out.  (Airline travel was one of the factors that made gays such efficient carriers.)  More drastic is quarantine: total isolation of infected individuals.  Like fire, a virus can burn itself out when there are no new ways to spread.  This is the origin of our tendency to stigmatize and shun infected people.  It works fine if you have no conscience or empathy for suffering.  But only if you really CAN isolate the carrier absolutely -- no one sneaking and and out on mercy missions.  If the carrier does suss the intention and run for it, thus spreading the virus.

The rest of this post is basic information about research into the tiny and puzzling interacting molecules of both the virus and our bodily defenses.  They cannot be seen without powerful equipment.  The appearance or suspected practices of humans will not reveal the presence of HIV.  Only tests can tell.  But the best defense against a virus of any kind is basic good health produced by nutrition, shelter, sleep, social support and so on.  Normally that will be enough for the immune system to take care of business.

I wish I could credit the people who wrote the wikipedia entries below.  I try to mark quotes with italic print.  I’ve left most of the links and url’s.

Simian immunodeficiency viruses (SIVs) are retroviruses able to infect at least 45 species of African non-human primates.[1][2] 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.[3][4]

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 human HIV-1 is “number one” because it was the first detected since it set off the epidemic among world humans.  Evidently simians and monkeys have been quietly dying in the jungle all along. This virus morphs as much as flu so it doubles back on itself and can affect a human with several versions at once, maybe even creating a hybrid, evolving to escape medicinal molecules.  Scientists have deliberately invented a hybrid virus, partly HIV and partly SIV.  They call it SHIV.  It’s a lab virus that never goes anywhere else.
The origins of viruses in the evolutionary history of life are unclear: some may have evolved from plasmids—pieces of DNA that can move between cells—while others may have evolved from bacteria. In evolution, viruses are an important means of horizontal gene transfer, which increases genetic diversity.[7] Viruses are considered by some to be a life form, because they carry genetic material, reproduce, and evolve through natural selection. However they lack key characteristics (such as cell structure) that are generally considered necessary to count as life. Because they possess some but not all such qualities, viruses have been described as "organisms at the edge of life".[8]

While not inside an infected cell or in the process of infecting a cell, viruses exist in the form of independent particles. These viral particles, also known as virions, consist of two or three parts: (i) the genetic material made from either DNA or RNA, long molecules that carry genetic information; (ii) a protein coat, called the capsid, which surrounds and protects the genetic material; and in some cases (iii) an envelope of lipids that surrounds the protein coat when they are outside a cell.


HIV is able to meddle with the epigenome to disguise itself or even turn off the host’s defenses, but it’s real goal is to insert itself into the chromosomes of the human cell itself.  It doesn’t wiggle into the same position each time.  Or necessarily in the same way.  Or it could settle into the epigenome itself. 

[You’ll need to keep the misspelling for this link to work.]

HIV infection also exploits the epigenome to achieve its viral latency, although its mechanism is through modifying DNA methylation.  HIV is capable of remaining latent during the most brutal of anti-viral assaults which led to investigations into the mechanism behind this. Researchers were able to show that HIV uses two CpG islands that flank its transcription start site in order to recruit the hosts MBD2 and HDAC2 and use it to achieve its deadly silencing. The team was able to add the icing to their cake by coaxing the virus out of hiding by treatment with 5aza (which leads to a loss of methylation).
[Methylation is how the epigenome turns genes on and off.]

Ultimately, it appears that epigenetic exploits are common and important molecular mechanisms that viruses rely on. While they don’t have their own epigenomes, viruses are more than capable of taking over for their host at every level of the epigenetic landscape to achieve some of their most devastating features, particularly viral latency.

A group at the Salk Institute pitted CRISPR against HIV. HIV is particularly hard to fight because it integrates into target cell genomes, where it can lie in wait, safe from standard drugs. What we really need to get rid of HIV is some way to specifically target its DNA sequence inside cells… oh wait, CRISPR!

The real challenge in HIV, though, is getting rid of viruses already integrated and hiding inside cells. The team tested Cas9 against these particularly dastardly proviruses by using cells with pre-integrated reporter viruses. Fourteen day after transient Cas9 transfection, about half the cells were GFP-free, and a second round of Cas9 expression cured about half of the remainder. This could be good for potential therapies, since multiple low-dose treatments may have fewer side effects for the patient. 

To make Cas9 an even more efficient HIV fighter, the group screened different target sites in the HIV genome and targeted two sites at once. With these improved versions, they not only cut the number of cells expressing viral GFP by 90%, they also saw about 4 times more cells surviving and thriving, suggesting the cells really had kicked the virus. HIV-immune Hematopoietic Stem Cells To test the system in even more relevant situations, the group stably integrated Cas9 into a human T-cell line and bathed them in HIV. Again, Cas9 protected the cells, even though most control cells were GFP-positive and/or dead within 14 days. Finally, they stably integrated Cas9 into human stem cells, differentiated them into white blood cells, and showed 90% immunity to HIV. These results suggest that where our own immune system fails, at least against HIV, maybe we can help it with one stolen from bacteria. 

AIDS remains incurable due to the permanent integration of HIV-1 into the host genome, imparting risk of viral reactivation even after antiretroviral therapy. New strategies are needed to ablate the viral genome from latently infected cells, because current methods are too inefficient and prone to adverse off-target effects. To eliminate the integrated HIV-1 genome, we used the Cas9/guide RNA (gRNA) system, in single and multiplex configurations. We identified highly specific targets within the HIV-1 LTR U3 region that were efficiently edited by Cas9/gRNA, inactivating viral gene expression and replication in latently infected microglial, promonocytic, and T cells. Cas9/gRNAs caused neither genotoxicity nor off-target editing to the host cells, and completely excised a 9,709-bp fragment of integrated proviral DNA that spanned from its 5′ to 3′ LTRs. Furthermore, the presence of multiplex gRNAs within Cas9-expressing cells prevented HIV-1 infection. Our results suggest that Cas9/gRNA can be engineered to provide a specific, efficacious prophylactic and therapeutic approach against AIDS.

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