LANL RESEARCHERS STUDY HIV VIRUS SPREAD WITH COMPUTER MODELING

FROM:  LOS ALAMOS NATIONAL LABORATORY
HIV Virus Spread and Evolution Studied Through Computer Modeling

LOS ALAMOS, N.M., November 19, 2013—Researchers at Los Alamos National Laboratory are investigating the complex relationships between the spread of the HIV virus in a population (epidemiology) and the actual, rapid evolution of the virus (phylogenetics) within each patient’s body.

“We have developed novel ways of estimating epidemics dynamics such as who infected whom, and the true population incidence of infection versus mere diagnoses dates,” said Thomas Leitner, principal investigator. “Obviously, knowledge about these things is important for public health monitoring, decision making and intervention campaigns, and further to forensic investigations.”

The team models the uninfected population using traditional differential equations on the computer; this is done for computational speed, because an agent-based component is much more demanding. Once a person is infected, he/she becomes an “agent” in computer modeling terms, and the model starts following their behavior individually, as well as the viral HIV evolution within the person.

Agent-based Modeling Clarifies Infection History

This new modeling approach distinguishes between susceptible and infected individuals to capture the full infection history, including contact tracing data for infected individuals. The uninfected individuals are modeled at a population level and stratified by transmission risk and social group. The social network in this model forms – and can change – during the simulation. Thus, the model is much more realistic than traditional models.

The advantage of this epidemiological model, Leitner said, is that “it allows us to simulate many possible outcomes of epidemics with known parameters of human interactions, where social networks form as part of the agent interactions. It is a flexible system that has the ability to describe realistic human populations.”

Within a National Institutes of Health-supported project “Reconstructing HIV Epidemics from HIV Phylogenetics,” the team has published 10 papers describing new mathematical models and results from real data addressing these issues. Most recently, they published a Nature correspondence on the limitations of HIV forensics and the need for better standards.

Who Infected Whom

A key question is on the fundamental limitations to the inference of who infected whom, based on a concept known as the pre-transmission interval (which this group first described back in 1999). Another publication, published in Epidemics, developed a new hybrid model to simulate and analyze the spread of HIV or other pathogens spread in a human population. The work also appeared in PLoS-ONE Public Library of Science online publication.

As an example, the team modeled a Latvian HIV-1 epidemic, and they showed that injecting drug users fueled the heterosexual population, thereby sustaining the overall epidemic. The researchers are now expanding this hybrid model to also include HIV genetic evolution, which occurs in every infected individual.

The researchers have shown that in fast HIV epidemics – such as among individuals injecting themselves with drugs – HIV viral evolution is slow, resulting in little diversification at the population level. Meanwhile, slower-spreading epidemics display more HIV evolution over the same amount of time.

New Field of Phylodynamics Evolves

Understanding HIV’s genetic evolution will soon allow investigations of how accurately researchers can reconstruct different epidemiological scenarios using pathogen genetic materials, an important and growing field called phylodynamics.

The team also has developed a new mathematical model that facilitates estimation of when a person was infected with HIV based on a previously used biomarker (BED IgG).

“This is important because most HIV infected persons are not discovered shortly after infection rather, they are often discovered long after, often years after infection, said Leitner. “Thus, to estimate true incidence, that is when infections actually occurred, cannot be done based on diagnosis dates.”

Using Swedish surveillance data, the team has shown that the common assumption that infection occurred on average half way between last negative test and first positive test, is wrong. Instead, the actual infection is strongly skewed towards the first positive sample.

This finding should have large impact on epidemiological models used worldwide by public health organizations, Leitner says. “Currently, we have further developed this model to also correct for unknown cases, such as infected people not yet discovered but who contribute to new infections and thereby the true incidence of the disease.”

The Team Behind the Insights

Researchers include Frederik Graw, Thomas Leitner, Ruy M. Ribeiro, and Helena Skar (Los Alamos National Laboratory) and Jan Albert (Karolinska Institute and Karolinska University Hospital). The National Institutes of Health funded the research.

THE PATTERNS NATURE OF PLANET EARTH AND LIFE

Photo:  Huricane Irene.  Credit:  NASA
FROM: NATIONAL SCIENCE FOUNDATION
Tale of Two Scientific Fields--Ecology and Phylogenetics--Offers New Views of Earth's Biodiversity
Patterns in nature are in everything from ocean currents to a flower's petal.
Scientists are taking a new look at Earth patterns, studying the biodiversity of yard plants in the U.S. and that of desert mammals in Israel, studying where flowers and bees live on the Tibetan plateau and how willow trees in America's Midwest make use of water.
They're finding that ecology, the study of relationships between living organisms and their environment, and phylogenetics, research on evolutionary relationships among groups of organisms, are inextricably intertwined.
Results of this tale of two fields are highlighted in a special, August 2012 issue of the journal Ecology, published by the Ecological Society of America (ESA). Most of the results reported are funded by the National Science Foundation (NSF).
The issue will be released at the annual ESA meeting, held this year from August 5-10 in Portland, Ore.
Melding information from ecology and phylogenetics allows scientists to understand why plants and animals are distributed in certain patterns across landscapes, how these species adapt to changing environments across evolutionary time--and where their populations may be faltering.
"To understand the here and now, ecologists need more knowledge of the past," says Saran Twombly, program director in NSF's Division of Environmental Biology. "Incorporating evolutionary history and phylogenies into studies of community ecology is revealing complex feedbacks between ecological and evolutionary processes."
Maureen Kearney, also a program director in NSF's Division of Environmental Biology adds, "Recent studies have demonstrated that species' evolutionary histories can have profound effects on the contemporary structure and composition of ecological communities."
In the face of rapid changes in Earth's biota, understanding the evolutionary processes that drive patterns of species diversity and coexistence in ecosystems has never been more pressing, write co-editors Jeannine Cavender-Bares of the University of Minnesota, David Ackerly of the University of California at Berkeley and Kenneth Kozak of the University of Minnesota.
"As human domination of our planet accelerates," says Cavender-Bares, "our best hope for restoring and sustaining the ‘environmental services' of the biological world is to understand how organisms assemble, persist and coexist in ecosystems across the globe."
Papers in the volume address subjects such as the vanishingly rare oak savanna ecosystem of U.S. northern tier states, revealing an ancient footprint of history on the savanna as well as how it has fared in a 40-year fire experiment.
Other results cover the influence of ecological and evolutionary factors on hummingbird populations; habitat specialization in willow tree communities; growth strategies in tropical tree lineages and their implications for biodiversity in the Amazon region; and the characteristics of common urban plants.
"The studies in this issue show that knowledge of how organisms evolve reveals new insights into the ecology and persistence of species," says Cavender-Bares.
Plants in urban yards, for example, are more closely related to each other--and live shorter lives--than do plants in rural areas, found Cavender-Bares and colleagues.
Their study compared plant diversity in private urban yards in the U.S. Midwest with that in the rural NSF Cedar Creek Long-Term Ecological Research site in Minnesota.
Cities are growing faster and faster, with unexpected effects, says Sonja Knapp of the Hemholtz Center for Environmental Research in Germany, lead author of the paper reporting the results.
"Understanding how urban gardening affects biodiversity is increasingly important," says Cavender-Bares. "Urbanites should consider maintaining yards with a higher number of species."
In the special issue, researchers also look at topics such as what determines the number of coexisting species in local and regional communities of salamanders. Kenneth Kozak of the University of Minnesota and John Wiens of Stony Brook University report that variation in the amount of time salamanders occupy different climate zones is the primary factor.
Evolution of an herbaceous flower called goldfields, and how that led to the plant's affinity for certain habitats, is the subject of a paper by David Ackerly, Nancy Emery of Purdue University and colleagues. Emery is the paper's lead author.