Understanding HIV's persistence

June 19, 2017, Brigham and Women's Hospital
HIV (yellow) infecting a human immune cell. Credit: Seth Pincus, Elizabeth Fischer and Austin Athman, National Institute of Allergy and Infectious Diseases, National Institutes of Health

Most cells in the human body have a limited lifespan, typically dying after several days or weeks. And yet, HIV-1 infected cells manage to persist in the body for decades. Current treatment for HIV is very effective at suppressing the virus, but is unable to entirely clear the disease, which can rapidly recur if treatment is ever stopped. A new study, published in the Journal of Clinical Investigation, led by Mathias Lichterfeld, MD, PhD, and Guinevere Lee, PhD, from the Brigham and Women's Hospital Infectious Disease Division sheds new light on the mechanism underlying the persistence of HIV-1 infected cells despite antiviral treatment.

"Our research points to a driving force that stabilizes the pool of HIV-infected in the host, which can persist lifelong despite very effective antiretroviral therapy," said Lichterfeld. "These findings have important implications for efforts to reduce or eliminate HIV from the body, including interventions like vaccines and checkpoint inhibitors."

Using a novel viral sequencing approach to track viral infection in different subtypes of CD4 T cells, this study found that a remarkable number of infected cells harbor sequences that are completely identical over the entire full-length viral sequence. Indeed, individual clusters of cells harboring such identical sequences were observed in roughly 60 percent of all memory CD4 T cells, the primary target cells for HIV. These data suggest that cells harboring identical viral sequences all stem from one particular CD4 T cell that presumably got infected prior to the beginning of antiviral therapy. That cell has gone on to disseminate and expand the HIV-infected cell pool whenever it divides, passing on the viral genetic material to its in a process called "clonal proliferation." By this mechanism, a single HIV-infected cell can, simply by dividing for 10-20 times, amplify the number of virally infected cells by up to a million fold.

"This work shows that HIV is taking a free ride: It effectively exploits the normal proliferative behavior of for propagation and dissemination of the viral genome," said Lee.

Interrupting or blocking proliferation of such virally-infected cells may represent a future strategy to limit viral persistence despite , and may someday allow for the development of novel clinical interventions, leading to a long-term, drug-free remission of HIV infection.

Explore further: Reservoirs of latent HIV can grow despite effective therapy, study shows

More information: Guinevere Q. Lee et al, Clonal expansion of genome-intact HIV-1 in functionally polarized Th1 CD4+ T cells, Journal of Clinical Investigation (2017). DOI: 10.1172/JCI93289

Related Stories

Reservoirs of latent HIV can grow despite effective therapy, study shows

May 30, 2017
Researchers at Johns Hopkins Medicine report new evidence that immune cells infected with a latent form of human immunodeficiency virus (HIV) are able to proliferate, replenishing the reservoir of virus that is resistant ...

Study identifies population of stem-like cells where HIV persists in spite of treatment

January 12, 2014
Although antiviral therapy against HIV suppresses viral replication and allows infected individuals to live relatively healthy lives for many years, the virus persists in the body, and replication resumes if treatment is ...

Researchers identify a new HIV reservoir

April 17, 2017
HIV cure research to date has focused on clearing the virus from T cells, a type of white blood cell that is an essential part of the immune system. Yet investigators in the Division of Infectious Diseases at the University ...

Study demonstrates how Zika virus rewires and repurposes invaded cells

March 30, 2017
New research reveals a high-resolution view of the Zika viral life cycle within infected cells and shows dramatic changes in the cell's architecture throughout the infection process. This novel perspective may lead to the ...

Reservoir divers: Select antiviral cells can access HIV's hideouts

January 31, 2017
When someone is HIV-positive and takes antiretroviral drugs, the virus persists in a reservoir of infected cells. Those cells hide out in germinal centers, specialized areas of lymph nodes, which most "killer" antiviral T ...

Immune-enhancing treatment may destabilize HIV reservoirs

July 21, 2016
Although antiretroviral therapy (ART) can reduce the amount of HIV in the blood to an undetectable level in most chronically infected people, it cannot eliminate reservoirs of HIV that persist in latently infected immune ...

Recommended for you

HIV-1 genetic diversity is higher in vaginal tract than in blood during early infection

January 18, 2018
A first-of-its-kind study has found that the genetic diversity of human immunodeficiency virus type 1 (HIV-1) is higher in the vaginal tract than in the blood stream during early infection. This finding, published in PLOS ...

War in Ukraine has escalated HIV spread in the country: study

January 15, 2018
Conflict in Ukraine has increased the risk of HIV outbreaks throughout the country as displaced HIV-infected people move from war-affected regions to areas with higher risk of transmission, according to analysis by scientists.

Researchers offer new model for uncovering true HIV mortality rates in Zambia

January 12, 2018
A new study that seeks to better ascertain HIV mortality rates in Zambia could provide a model for improved national and regional surveillance approaches, and ultimately, more effective HIV treatment strategies.

New drug capsule may allow weekly HIV treatment

January 9, 2018
Researchers at MIT and Brigham and Women's Hospital have developed a capsule that can deliver a week's worth of HIV drugs in a single dose. This advance could make it much easier for patients to adhere to the strict schedule ...

New long-acting, less-toxic HIV drug suppresses virus in humanized mice

January 8, 2018
A team of Yale researchers tested a new chemical compound that suppresses HIV, protects immune cells, and remains effective for weeks with a single dose. In animal experiments, the compound proved to be a promising new candidate ...

Usage remains low for pill that can prevent HIV infection

January 8, 2018
From gritty neighborhoods in New York and Los Angeles to clinics in Kenya and Brazil, health workers are trying to popularize a pill that has proven highly effective in preventing HIV but which—in their view—remains woefully ...

0 comments

Please sign in to add a comment. Registration is free, and takes less than a minute. Read more

Click here to reset your password.
Sign in to get notified via email when new comments are made.