Though it looks more like a radioactive piece of Flubber slowly forcing itself into some unsuspecting globular structure, a new 37-second film clip ‘mdash; captured by researchers at UC Davis and the Mount Sinai School of Medicine ‘mdash; shows an HIV-infected T-cell spreading the virus to an uninfected T-cell.
The footage proves that the process occurs through a virological synapse: a cell-to-cell adhesion that allows the virus to transfer without leaving the safety of cell membranes.
A March 6 article in Science magazine challenged academics, industry specialists, patient advocates and government officials to cooperate in the search for a vaccine for the global killer; the video footage’s resulting report ran in the same publication on March 27.
When screened at an HIV conference this summer, the transfer elicited ‘audible gasps’ from the audience, said Thomas Huser, associate professor and chief scientist at the UC Davis Center for Biophotonics Science and Technology.
‘The filming of live cells was important because it allowed us to make very specific physical measurements with regard to the rate of transfer of viral proteins in the already infected cell, as well as in the newly infected target cells,’ Huser said. ‘This enables us to make more definitive conclusions about the nature of the virus transfer. It allows others to develop better models of the pathway of cell-cell transmission, and, of course, it created some stunning visual imagery, which should be eye opening to scientists and the wider public alike.’
Highly active antiretroviral therapy ‘mdash; the current go-to drug cocktail designed to halt HIV replication ‘mdash; still has significant drawbacks. It is an expensive, lifelong prescription with long-term side effects in older HIV-positive patients that can include certain types of cancer, heart disease, liver disease and diabetes.
Like Huser, many researchers believe that HIV treatments have reached a point where it is necessary to put treatment research on the back burner in favor of discovering a vaccine.
‘ ‘Clearly one of the highest priorities of AIDS research, in addition to finding a cure, is to find an effective preventive vaccine,’ said Benjamin Chen, assistant professor at the Mount Sinai School of Medicine. Chen’s laboratory created the green fluorescent virus technology, like a food coloring for cells, used to illuminate the cell-to-cell transfer in the video.
Chen noted tha
t the new evidence may assist researchers in creating an effective HIV vaccine, by emphasizing the need for antibodies that attack both modes of transmission ‘mdash; cell-to-cell along with the previously accepted cell-free transmission through plasma.
UCSD professor of pathology and medicine Douglas Richman ‘mdash; who also serves as director of the Center for AIDS Research at UCSD ‘mdash; said the goal of current HIV/AIDS research is to reduce the need for chronic suppressive therapy by eliminating the latent reservoir of HIV infection, the pool of infection that remains dormant. However, this would demand additional knowledge of possibly undiscovered HIV ‘reservoirs,’ as well as a greater understanding of HIV activities in the bloodstream.
According to Chen the next goal is discovering how to stop the virus from spreading by using synapses, as well as development of a method to help the immune system produce significant amounts of HIV-blocking antibodies.
‘We hope that this work will trigger significantly more work on the importance of direct cell-cell transmission for HIV, because we believe that this could be one of the reasons why current attempts at developing a vaccine have been unsuccessful because the virus in essence hides inside cells,’ Huser said.
But shortages in research funding from the federal government, coupled with a need for a full-time virologist ‘mdash; currently compensated for by Chen’s research group ‘mdash; might slow progress. Other problems include the skeptical response of the HIV research community and the pharmaceutical industry.
Huser also realizes the problems researchers are faced with in attempts to cure the disease.
‘There are still many mysteries surrounding HIV spread,’ Huser said. ‘We don’t know if spread through direct cell-cell transfer is really the dominant mode for how the infection spreads in the body. At the current point, we can only hypothesize that it is. There is also a big mystery surrounding the actual infection of target cells. We found that the virus in the target cell appears to be contained in a cellular compartment, similar to an endosome. We currently have no clue about how HIV is able to get out of this compartment.’
Scientists are still not overly optimistic when it comes to the future of HIV/AIDS research and vaccine discovery; they acknowledge several problems that hinder progress. One is time. Some, like Richman, believe that given the length of time required to complete other treatments, the process will be a tedious and slow-moving one that may not produce results for years, if not decades.
‘This virus is different from almost any other virus,’ Richman said. ‘There is so much antigenic variation that it will be difficult to create a vaccine for this. It’s going to be a long, hard struggle.’
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