MS drug may be used to inhibit HIV infection and reduce latent reservoir


Date:
August 13, 2020
Source:
George Washington University
Summary:
A multiple sclerosis drug may be used to block HIV infection and
reduce the latent reservoir, according to new research.



FULL STORY ========================================================================== Fingolimod, an FDA-approved immunosuppressive drug used to treat multiple sclerosis flare-ups, may be used to block HIV infection and reduce the
latent reservoir. Researchers at the George Washington University (GW) published their novel findings in PLOS Pathogens.


========================================================================== "While antiretroviral drugs have been effective in treating HIV thus
far, drug resistance, negative side effects of antiretroviral therapy,
and its varying efficacy underscore the need to develop alternative
treatment and prevention options," said Alberto Bosque, PhD, MBA,
assistant professor of microbiology, immunology, and tropical medicine
at the GW School of Medicine and Health Sciences. "For the first
time, our research team found that by targeting the receptors to the
signaling molecule Sphingosine-1-phosphate (S1P), we could effectively
block HIV infection and cell-to-cell transmission of the virus and
consequently reduce the seeding of the latent virus in the test tube." Treatment for HIV is lifelong, due to a latent reservoir of HIV-infected
cells that may reactivate at any time. In addition to other drawbacks,
current antiretroviral therapies do not specifically target latent
infection. Finding ways to not only target infection, but also reduce
the latent reservoir would have a great impact on the nearly 40 million
people living with HIV worldwide.

Fingolimod, known also as Gilenya, works by acting as a functional
antagonist of S1P receptors. By observing human immune cells, Bosque and
his research team found that HIV infection was blocked by targeting S1P receptors with Fingolimod. The team discovered that the HIV life cycle
was impacted at multiple levels. First, the drug reduced the surface
density of the HIV receptor in T-cells, inhibiting viral binding and
fusion. Secondly, Fingolimod activated the antiviral restriction factor
SAMHD1, leading to a reduction in levels of total and integrated HIV.

"We believe this compound may be a promising novel therapy for HIV
treatment and prevention," said Bosque.


========================================================================== Story Source: Materials provided by George_Washington_University. Note:
Content may be edited for style and length.


========================================================================== Journal Reference:
1. Rachel S. Resop, Re'mi Fromentin, Daniel Newman, Hawley Rigsby,
Larisa
Dubrovsky, Michael Bukrinsky, Nicolas Chomont, Alberto
Bosque. Fingolimod inhibits multiple stages of the HIV-1
life cycle. PLOS Pathogens, 2020; 16 (8): e1008679 DOI:
10.1371/journal.ppat.1008679 ==========================================================================

Link to news story: https://www.sciencedaily.com/releases/2020/08/200813142339.htm

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