Nav: Home

HIV spreads through direct cell-to-cell contact

July 25, 2019

The spread of pathogens like the human immunodeficiency virus (HIV) is often studied in a test tube, i.e. in two-dimensional cell cultures, even though it hardly reflects the much more complex conditions in the human body. Using innovative cell culture systems, quantitative image analysis, and computer simulations, an interdisciplinary team of scientists from Heidelberg University has now explored how HIV spreads in three-dimensional tissue-like environments. The researchers' results show that the tissue structure forces the virus to spread through direct cell-to-cell contact.

Despite over 30 years of research, many key aspects of how HIV, the causative agent of the acquired immune deficiency syndrome (AIDS) spreads are still not understood. One of these unresolved questions concerns the interactions between the virus with the environment in the human body. Traditionally it has been assumed that infected cells release viral particles which then diffuse and eventually infect other cells. But it is also possible that viral particles are directly transferred from one infected cell to the next through close contact. Until now it was unknown which of these modes of transmission prevailed in tissue. "Studies on HIV replication in the lab are mostly conducted in simple cell culture experiments in plastic dishes that do not reflect the complex architecture and heterogeneity of tissue", explains study director Prof. Dr Oliver Fackler of the Center for Integrative Infectious Disease Research (CIID) at Heidelberg University Hospital.

In their approach, the Heidelberg researchers took into account that the so-called CD4 T helper cells, the preferred cell type infected by HIV, are highly motile in their physiological environment. They used a novel cell culture system, in which a three-dimensional scaffold was generated with the help of collagen. This allowed for maintaining the cells' mobility and monitoring primary CD4 T cells infected with HIV-1 in a tissue-like environment over the course of several weeks. Using this innovative approach, the researchers measured a number of factors that characterise cell motility, virus replication, and the gradual loss of CD4 T helper cells. "This yielded a very complex set of data that was impossible to interpret without the help from scientists of other disciplines", explains Dr Andrea Imle, who worked on the project during her PhD at the CIID.

In analysing the data, the scientists who conducted the experiments collaborated with colleagues from the fields of image processing, theoretical biophysics and mathematical modelling. Together they were able to characterise the complex behaviour of cells and viruses and simulate it on the computer. This made it possible to make important predictions on the key processes that determine HIV-1 spread in these 3D cultures, which were confirmed by subsequent experimentation. "Our interdisciplinary study is a good example of how iterative cycles of experimentation and simulation can help to quantitatively analyse a complex biological process", states Prof. Dr Ulrich Schwarz of the Institute for Theoretical Physics at Heidelberg University.

The data analysis revealed that the 3D environment of the cell culture system suppresses infection with a cell-free virus while simultaneously promoting direct virus transmission from cell to cell. "Our models allowed us to integrate short single-cell microscopy films with long-term cell population measurements and thereby to estimate the minimal time span required for cell-to-cell contacts to transmit infection", explains Dr Frederik Graw of the BioQuant Centre of Heidelberg University. The researchers hope that these findings will eventually lead to new therapeutic approaches in the treatment of HIV.
-end-
The research was conducted within the Collaborative Research Centre "Integrative Analysis of Pathogen Replication and Spread" (CRC 1129) funded by the German Research Foundation and supported by the Center for Modelling and Simulation in the Biosciences (BIOMS) of Heidelberg University. The results were published in Nature Communications.

University of Heidelberg

Related Hiv Articles:

The Lancet HIV: Study suggests a second patient has been cured of HIV
A study of the second HIV patient to undergo successful stem cell transplantation from donors with a HIV-resistant gene, finds that there was no active viral infection in the patient's blood 30 months after they stopped anti-retroviral therapy, according to a case report published in The Lancet HIV journal and presented at CROI (Conference on Retroviruses and Opportunistic Infections).
Children with HIV score below HIV-negative peers in cognitive, motor function tests
Children who acquired HIV in utero or during birth or breastfeeding did not perform as well as their peers who do not have HIV on tests measuring cognitive ability, motor function and attention, according to a report published online today in Clinical Infectious Diseases.
Efforts to end the HIV epidemic must not ignore people already living with HIV
Efforts to prevent new HIV transmissions in the US must be accompanied by addressing HIV-associated comorbidities to improve the health of people already living with HIV, NIH experts assert in the third of a series of JAMA commentaries.
The Lancet HIV: Severe anti-LGBT legislations associated with lower testing and awareness of HIV in African countries
This first systematic review to investigate HIV testing, treatment and viral suppression in men who have sex with men in Africa finds that among the most recent studies (conducted after 2011) only half of men have been tested for HIV in the past 12 months.
The Lancet HIV: Tenfold increase in number of adolescents on HIV treatment in South Africa since 2010, but many still untreated
A new study of more than 700,000 one to 19-year olds being treated for HIV infection suggests a ten-fold increase in the number of adolescents aged 15 to 19 receiving HIV treatment in South Africa, according to results published in The Lancet HIV journal.
Starting HIV treatment in ERs may be key to ending HIV spread worldwide
In a follow-up study conducted in South Africa, Johns Hopkins Medicine researchers say they have evidence that hospital emergency departments (EDs) worldwide may be key strategic settings for curbing the spread of HIV infections in hard-to-reach populations if the EDs jump-start treatment and case management as well as diagnosis of the disease.
NIH HIV experts prioritize research to achieve sustained ART-free HIV remission
Achieving sustained remission of HIV without life-long antiretroviral therapy (ART) is a top HIV research priority, according to a new commentary in JAMA by experts at the National Institute of Allergy and Infectious Diseases (NIAID), part of the National Institutes of Health.
First ever living donor HIV-to-HIV kidney transplant
For the first time, a person living with HIV has donated a kidney to a transplant recipient also living with HIV.
The Lancet HIV: PrEP implementation is associated with a rapid decline in new HIV infections
Study from Australia is the first to evaluate a population-level roll-out of pre-exposure prophylaxis (PrEP) in men who have sex with men.
Researchers date 'hibernating' HIV strains, advancing BC's leadership in HIV cure research
Researchers have developed a novel way for dating 'hibernating' HIV strains, in an advancement for HIV cure research.
More HIV News and HIV Current Events

Trending Science News

Current Coronavirus (COVID-19) News

Top Science Podcasts

We have hand picked the top science podcasts of 2020.
Now Playing: TED Radio Hour

Listen Again: Meditations on Loneliness
Original broadcast date: April 24, 2020. We're a social species now living in isolation. But loneliness was a problem well before this era of social distancing. This hour, TED speakers explore how we can live and make peace with loneliness. Guests on the show include author and illustrator Jonny Sun, psychologist Susan Pinker, architect Grace Kim, and writer Suleika Jaouad.
Now Playing: Science for the People

#565 The Great Wide Indoors
We're all spending a bit more time indoors this summer than we probably figured. But did you ever stop to think about why the places we live and work as designed the way they are? And how they could be designed better? We're talking with Emily Anthes about her new book "The Great Indoors: The Surprising Science of how Buildings Shape our Behavior, Health and Happiness".
Now Playing: Radiolab

The Third. A TED Talk.
Jad gives a TED talk about his life as a journalist and how Radiolab has evolved over the years. Here's how TED described it:How do you end a story? Host of Radiolab Jad Abumrad tells how his search for an answer led him home to the mountains of Tennessee, where he met an unexpected teacher: Dolly Parton.Jad Nicholas Abumrad is a Lebanese-American radio host, composer and producer. He is the founder of the syndicated public radio program Radiolab, which is broadcast on over 600 radio stations nationwide and is downloaded more than 120 million times a year as a podcast. He also created More Perfect, a podcast that tells the stories behind the Supreme Court's most famous decisions. And most recently, Dolly Parton's America, a nine-episode podcast exploring the life and times of the iconic country music star. Abumrad has received three Peabody Awards and was named a MacArthur Fellow in 2011.