THE INEVITABLE may have already come, but justly, the antidote is on its way.
With the advent of molecular science, a scientific discipline that deals with the interactions of various genes and proteins in cells, explaining the origin of several human diseases and creating strategies to improve healthcare.
Resident researchers from the Research Center for the Natural and Applied Sciences presented current innovations and discoveries in low-cost technologies for disease diagnostics and clean energy applications of nanomaterials. With them were scientists from Nagoya City University (NCU) who discussed the present status in the development of treatments for acquired immunodeficiency syndrome (AIDS), during the first UST-NCU Symposium on Molecular Sciences held at the Civil Law Auditorium last Nov. 25.
Invisible, yet invincible
According to Medscape, human immunodeficiency virus (HIV) is a blood-borne virus typically transmitted via sexual intercourse or shared intravenous drug paraphernalia like syringes and mother-to-child transmission, which can occur during the birth process or during breastfeeding.
The disease is caused by infection with HIV-1 or HIV-2, which are two common strains of retroviruses, which use ribonucleic acid (RNA) as their genetic material. As RNA viruses like HIV mutate at a faster rate, the strains are more resistant to a number of widely-available therapies.
The virus targets a person’s immune system by combining its genetic material with the host’s DNA. Afterward, it replicates itself in infected cells which proliferate inside the body.
Infection with HIV results in cellular immune deficiency characterized by the depletion of CD4+ cells, also known as helper T cells, which help the activity of the immune system in fighting foreign entities inside the body.
Moreover, the loss of these cells leads to the development of opportunistic infections caused by bacteria or viruses which initially may not pose a threat to the human health until the immune system has been completely compromised—rendering the infected individual positive toAIDS.
Next-generation sequencing
Despite the global effort of scientists to combat the elusive virus, cases of HIV/AIDS continue to increase worldwide and finding the cure is yet to be discovered.
An emerging field known as bioinformatics incorporates molecular biology, engineering and computer sciences as a tool for faster detection and control of AIDS—with the use of supercomputers in monitoring how different strains of HIV mutate and interact inside the body.
“Problems regarding the emergence of drug-resistant viral variants are inevitable,” said Dr. Takashi Okamoto, chairman of the Department of Molecular and Cellular Biology at NCU.
Okamoto stressed the importance of bioinformatics in research studies concerning HIV/AIDS because it will help scientists design plausible drug interventions using computer simulations of different interactions between genes and proteins that affect the replication and expression of the disease in a person’s body.
“Knowing the disease is one thing and finding the cure is another,” he said.
Okamoto noted that since the completion of the Human Genome Project in 2003, an international research collaboration intended to determine the full genetic make-up of human beings, a wealth of information about the genes responsible for different diseases have been discovered, and scientists are trying to find ways to obtain useful information from the genome sequences of humans and HIV-1.
One of the most studied cellular molecules in bioinformatics analysis related to HIV-1 infection are microRNAs.
According to Neil Tan Gana, a Filipino molecular biologist from NCU, a microRNA is a small non-coding RNA molecule essential for the antiviral responses of an individual against viruses.
Once the microRNA of a human host makes a perfect match with the messenger RNA (mRNA) of HIV-1, an effective gene silencing will occur and viral expression and replication in the host will be prevented.
“The keyword is the perfect match [between human microRNA and viral mRNA] will become, then the more effective the silencing will be,” Tan Gana said.
Gene silencing has been a promising technique to prevent the expression and replication of viral genes responsible for the fatal effects of the disease to a patient’s immune system.
However, Tan Gana also explained that HIV-1 can also encode viral microRNA which modifies the defense mechanisms of humans by creating an environment favorable for viral invasion and replication in the host cell. These types of microRNAs are also involved in viral latency among infected individuals.
Viral latency is a type of infection wherein the pathogenic virus enters the host and remains dormant over a period of time.
During this window of time, blood tests of an infected person tend to show no signs of HIV infection due to the lack of expression caused by the HIV-1 microRNA, posing a challenge to the eradication of the virus.
Tan Gana emphasized the factors that should be addressed in creating models for gene silencing of HIV-1.
“For HIV, the analytical framework would be the effects of viral microRNAs in the virus itself, the second interaction will be the viral microRNA causing effects to the host cell messenger RNA (mRNA) and the third and fourth scenarios will be effects of the host microRNA when it suppresses the viral microRNA and the host cell mRNA,” he said.
The ‘bony’ paradox
Meanwhile, a drug compound used as medication for osteoporosis has also been found to cause a decline in bone minerals which leads to painful bone fractures.
Such paradox has been investigated by Marilyn Rimando, a biology professor at the College of Science in her study “The Role of Dexamethasone on the Osteogenic Differentiation of Mesenchymal Stem Cells.”
Dexamethasone belongs to the glucocorticoid steroid compounds used in treatments for rheumatic diseases like osteoporosis due to its ability to promote osteogenesis orbone formation among stem cells.
“The paradox is that we use glucocorticoid to induce differentiation of mesenchymal stem cells, however, prolonged administration and high concentrations of glucocorticoid can also lead to osteoporosis,” Rimando said.
The initial results of her study showed that dexamethasone boosted bone differentiation and formation only at the early stage of bone development but prolonged treatment decreases the potential of stem cells to mature into functional bone cells at the latter stage of development.
In addition, Rimando pointed out that a candidate gene called HDAC6 might also be responsible for the repression in the late stage of bone differentiation.
But despite the findings, Rimando admitted that there are still underlying mechanisms behind this phenomenon that should be further investigated at the molecular level.
“There are still a lot to explore and learn about the molecular mechanisms of dexamethasone in promoting osteogenesis,” she said.
