Africa Health Research Institute (AHRI) scientists have answered a longstanding question about how fast HIV spreads at the cellular level.
The new research is published in the scientific journal PLOS Pathogens.
While much is known about how the HIV virus transmits, the factors influencing how fast HIV multiplies or expresses within a single cell are less well understood. AHRI scientists were interested in discovering whether the virus ‘speeds up’ under certain circumstances. In other words, whether some types of HIV infection between cells result in an HIV virus cycle time – the time which elapses between a cell being infected, to that cell infecting another cell – which is faster than the two days usually measured for HIV.
Researchers led by Mikaël Boullé from AHRI’s Sigal Lab used time-lapse microscopy, which is time-lapse photography applied at the microscopic level, together with image and quantitative analysis to pinpoint when infected cells started to produce the virus.
Their findings show that the virus cycle time varies, and depends on the number of viruses infecting a cell. Alex Sigal explains that it’s a ‘first past the post’ mechanism, where the time of virus expression is the time that the fastest virus takes to express itself.
“If you’ve got 10 viruses infecting a cell, they could hypothetically do a few different things: firstly, they could interact with each other and make expression faster, secondly, they could interact and slow each other down, or thirdly, not interact – and each have different timing. This last option is exactly what happens. So if you have 10 viruses, the time of virus expression is the expression of the fastest virus. It would be the same if you infected 10 different cells with one virus each, and took the fastest among these as your infection time. This is very surprising; we thought that the viruses would cooperate, but they don’t,” he said.
“However, the bottom line is that by having multiple viruses transmitted between cells, the timing of the HIV viral cycle is accelerated. This type of multiple virus transmission happens in a specific mode of HIV infection called cell-to-cell spread, where the virus takes advantage of interactions between cells to jump in large numbers between an infected cell and the yet uninfected cell which is interacting with it.”
Their findings potentially start to explain how HIV infection is able to establish itself so quickly to become irreversible and why antiretroviral drugs, even when administered several days after HIV infection, can control but not cure the infection.
In partnership with surgeons from Durban’s Inkosi Albert Luthuli Central Hospital, the Sigal Lab now plans to test their findings in cells from lymph nodes donated by HIV infected patients to see how fast clinical infection can spread between cells, and whether it depends on the number of viruses that the cells transmit to each other.
*Read the paper here, and find out more about the Sigal Lab here.
(Top photo: This image shows the use of time-lapse microscopy combined with fluorescent reporters for HIV to determine the onset of infection. Newly infected cells are shown in yellow.)