Living with HIV/AIDS

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Human immunodeficiency virus (HIV) has infected millions of people and taken many lives.

Recent estimates suggest that 30- 36 million people worldwide are living with HIV/AIDS (avert). HIV is a virus that attacks the immune system and eventually causes AIDS. It infects peoples T-cells which are used by our immune system in order to fight diseases, so it's very obvious why this is a serious condition because it immediately attacks the very specific cells which are responsible for protecting our bodies. The virus penetrates the T-cell and transforms the cell using its genetic material. The HIV virus then forces the cells DNA to start the process of replicating new HIV. The cell then continues making more of the HIV virus and eventually releases them all after the cell dies, causing the new group HIV virus to go on and infect other cells and repeat the same process over and over again. This eventually causes our immune system to crumple because of the increasing number of T-cells dying due to the infection by the HIV virus. As the immune system becomes weaker we are more vulnerable to infections which we normally aren't with a healthy immune system.

There have been many different wide-ranging efforts do develop vaccines for the virus with none resulting in being effective. Antiretroviral drugs have indeed significantly benefited people who are infected with HIV but they have had an insignificant impact on the epidemic globally. In the peer reviewed research article Reawakening Retrocyclins: Ancestral Human Defensins Active Against HIV-1 a group of scientists have determined that theta-definsins called "retrocyclins" are effective inhibitors of the HIV-1 infection. Retrocyclins are antimicrobial agents which are powerful against bacteria and virus infections. These very genes are found in monkeys and protect them from dangerous viruses such as HIV. Retrocyclins belong to a group of proteins called defensins which protect the body against viruses and bacteria. Defensins include alpha, beta, and theta defensins. Theta-defensins are where retrocyclins are found in the white blood cells of monkeys such as baboons and orangutans. The group of scientists found that humans have the genes that are 90% similar to those that are found in the monkeys. The problem with the human genes though is that in humans the genes don't work as they do in monkeys. It is suggested that through evolution the gene mutated and a premature termination codon in the signal peptide part of the human retrocyclin mRNA prevents it translation. This mutation is referred to as a "nonsense mutation". A nonsense mutation occurs when a base in the genetic coding area of DNA is altered or changed causing the triplet code for its amino acid to become a stop codon. When a ribosome comes across a stop codon it stops adding any amino acids, causing the mRNA strand to be shorter than it should really be. The first challenge the scientists faced was to experiment with the human gene and see if they can alter or fix the mutation, then the next challenge was to figure out if the human cells can produce the retrocyclin protein from the gene after the mutation was mixed, and finally to see if it is affective against the HIV virus in humans. The scientists found a way to fix the mutation in the gene with a process involving gene transfer and using simple antibiotics. They where successful in finding a way to fix the mutation and were eager to go on to the next step and find out if the corrected gene can now produce the retrocylin protein.

In order to do this the group of scientists decided to insert the new version of the retrocyclin gene into human promyelocytic cells and tested to see if the protein was produced. "To determine if human cells have retained the ability to process ?-defensins, we transfected promyelocytic HL60 cells with retrocyclin constructs each encoding a nonapeptide in which the premature termination codon was replaced with a glutamine (?17Q). Results indicate that biologically active recombinant retrocyclin peptides can be synthesized in human promyelocytic cells"(plosbiology).

The scientists found that the corrected version can actually make the protein which was indeed similar to the version found in monkeys, now the next step was to continue further testing and see if the proteins are affective against blocking HIV infection.

Amazingly the samples from the human promyelocytic cells containing the fixed gene could in fact actually reduce HIV growth. This find is amazing because it suggests that humans contain the genes and the potential to protect ourselves from HIV.

The scientist in this experiment refer to our inability to produce retrocyclin naturally as a "disorder", one we inherited through evolution and one which has an incidence of 100% since all humans cannot produce retrocyclin. This experiment was in a way "curing" our disorder of producing retrocyclin which in turn results as an optimistic pathway to finding a cure for HIV infections. The experiment proves that we as humans do indeed posses the required machinery to produce retrocyclin, except the instructions to do so our not correct and need to be fixed. In the experiment the recorded data shows that at the end of the experiment the retrocyclins produced by human cells were 80% affective in preventing HIV from infecting further cells in the body and also reduced the amount of virus in certain cells which were already infected.

The findings in this experiment are very promising and should raise the morale and hope of many people around the world especially those who are already infected with the HIV virus. On the other hand it should be fairly obvious to all these people that the process involved, such as gene transfer, are not easy and inexpensive procedures. This situation will most likely become a problem in poor regions of the world such as Africa, where the HIV virus is most widespread among people. The obvious solution to this problem is of course a more inexpensive way to reactivate the ability to produce retrocyclin in humans. The good news is that the scientists involved in this experiment realized this and have come across ideas which may be very helpful. A possible solution they came across involves creating an aminoglycoside-based cream which could be used to prevent HIV infections. Aminoglycosides are what the scientists used in their experiment as an antibiotic along with gene transfer in order to make all this possible. Aminoglycosides in itself can cause errors when RNA transcribes information from DNA to make proteins(io9). In humans they cause the protein making machinery in our cells to make mistakes. This "mistake" actually works in our favor because this is what causes the machinery to continue through the mutation which originally would cause the retrocyclins in humans to be built incomplete. The mistake caused by the aminoglycosides helps humans produce full-length retrocyclin protein.