Tracking the cells that host HIV
Two phases of viral decline, now understood more clearly

Date:
February 3, 2022
Source:
DOE/Los Alamos National Laboratory
Summary:
New research sheds light on the lifespans and location of the cells
that are responsible for producing HIV, preventing its eradication.

Understanding the cells' dynamics may help scientists develop
new ways to reduce their number with the ultimate goal of curing
HIV infection.



FULL STORY ==========================================================================
New research sheds light on the lifespans and location of the
cells that are responsible for producing HIV, preventing its
eradication. Understanding the cells' dynamics may help scientists
develop new ways to reduce their number with the ultimate goal of curing
HIV infection.


========================================================================== "When chronically HIV-1 infected individuals are put on potent
antiretroviral drug therapy, the amount of virus in their blood
decreases," said Los Alamos National Laboratory Senior Fellow Alan
Perelson. He and collaborator David D.

Ho, MD, now at Columbia University School of Medicine, found that
"the viral decline occurred in two distinct phases, a fast first phase
followed by a slow second phase." Using a mathematical model of viral infection and treatment developed by Perelson, the team concluded that
the two-phase decline reflected the fact that HIV infected two distinct
cell populations that produced HIV. One population produced the majority
of the virus, but lived only a day or so. The decay of this population according to the model was responsible for the first phase decline of
the virus in the blood.

The second cell population, which released virus at a slower rate,
lived a matter of weeks while producing virus, and their loss according
to the model was responsible for the second phase of viral decay seen
in the blood.

Now, in a new paper published in the journal PNAS this week, Robert
Siliciano, MD, from Johns Hopkins University School of Medicine and his
team working with Perelson and Ruy Ribeiro from the Theoretical Biology
and Biophysics Group at Los Alamos National Laboratory searched for
these hypothesized cells with different decay rates. Siliciano's group
isolated HIV-infected cells in the blood of 17 people living with HIV on antiretroviral therapy twice a month for the first three months after the initiation of the therapy, and then every month for a year. They found
that very few of the short-lived infected cells responsible for the first
phase of viral decay were circulating in the blood, suggesting that these
cells most likely reside in tissues, such as lymph nodes and the spleen.

Instead, they found cells in the blood that carried an intact HIV
genome and which decayed with a half-life of about two weeks. These are presumably the cells responsible for the second phase of viral decay
predicted by Perelson and Ho. After about three months on treatment,
the remaining infected cells with intact HIV genomes decayed even more
slowly, now with a half-life of about 19 months. These cells may become
part of the latent-infected cell reservoir, which if therapy is stopped re-seeds the infection and virus then becomes detectable usually in a
matter of weeks.

The funding: National Institutes of Health (NIH) ========================================================================== Story Source: Materials provided by
DOE/Los_Alamos_National_Laboratory. Note: Content may be edited for
style and length.


========================================================================== Journal Reference:
1. Jennifer A. White, Francesco R. Simonetti, Subul Beg, Natalie
F. McMyn,
Weiwei Dai, Niklas Bachmann, Jun Lai, William C. Ford, Christina
Bunch, Joyce L. Jones, Ruy. M. Ribeiro, Alan S. Perelson, Janet
D. Siliciano, Robert F. Siliciano. Complex decay dynamics of
HIV virions, intact and defective proviruses, and 2LTR circles
following initiation of antiretroviral therapy. Proceedings of
the National Academy of Sciences, 2022; 119 (6): e2120326119 DOI:
10.1073/pnas.2120326119 ==========================================================================

Link to news story: https://www.sciencedaily.com/releases/2022/02/220203161215.htm

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