A thing of the past

By | Science & Technology
The HIV pathogen infecting cells.Credit@img.medicalxpress.com

A new study has found new inhibitor drugs prevent immature HIV cells from developing into mature HIV cells. This may represent a way forward by impeding replication into other healthy cells and preventing the development of AIDS.

Around 38 million individuals worldwide have HIV. The highest numbers exist in Africa, particularly South Africa, Swaziland, Zimbabwe and Nigeria. These numbers have decreased due to education of the public and the introduction of antiretroviral therapy (ART). Life expectancies in this region have significantly increased from 49.2 years to 60.5 years over the last two decades due to this. Today HIV has a presence in many Western countries and a new treatment or preventative measure may still be needed.

When HIV replicates its genetic structure, it may be variable in making most treatments ineffective. It has a long incubation period, appearing 2- 4 weeks later as influenza and then entering a dormant phase for up to 10 years. HIV transfers DNA into a host cell evading the detection of immune cells and becoming latent in the process. HIV then infects immune cells and when particular cells drop below a certain level, immunity becomes inactive.

This is why HIV leads to a reduction in the ability of the immune system eventually presenting as AIDS. HIV may be present in the cells in two forms; immature and mature. The immature form develops inside a cell; to affect another cell it has to transform into a mature form. This ability is examined in a new study. The team discovered an immature HIV cell may only change to a mature type when enzymes alter its anatomy. The immature cell has to develop to an important stage where a particular point and structure is exposed and may be severed, then enzymes re-construct the proteins to create a mature HIV cell.

Using a type of imaging called cryo-electron tomography and subtomogram averaging the team were able to observe the transition of a HIV cell from immature to mature in 3D. The important site is in a hidden position within immature cells where enzymes are far from able to sever the point. The team also observed the workings of new drugs which inhibit this maturation process to explain how they work. The effect of these drugs means this machinery may be unreachable by enzymes, the drug prevents it. However, the HIV pathogen has other strategies; genetic mutations alter the structure of certain cells allowing it to circumvent the inhibition from the drug. This means certain cells become resistant to the drug.

“Observing HIV when it had one of these inhibitor drugs on it, it was found the inhibitor far from allows the cutting machinery to get in, as may be expected,” says Florian Schurr. “Rather, the drug locks the immature HIV structure in place, so it evades being cut.” “Rather than preventing the drug from binding, the Pathogen becomes resistant through mutations which destabilise the immature structure,” says Kraussllich. “This allows it to rearrange and be cut even when the drug is in place.”

The aims with these findings may stimulate newer treatments, the team seems keen to examine the drugs and HIV in detail to support this objective. This may elucidate how the drugs attach to viral proteins and lead to improved drugs with the ability to prevent the HIV pathogen maturing and resulting in AIDS. Newer technologies may also support the understanding of the HIV maturation process, as in the combination of cryo-electron tomography and subtomogram technologies did in this study. Optimism may derive from this study as new ideas and understandings have been gleaned from the findings. Further understandings of the key proteins Capsid and SP1 and how these structures become stabilised by maturation inhibitors (drugs) may also produce different ideas into the prevention of AIDS. Many questions still need to be answered, over time a solution to HIV may appear, making it and AIDS a thing of the past.

How did the HIV/AIDS condition evolve?

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