Raging epidemics are old news to Prof. David Russell, microbiology and immunology, and his senior postdoc student David Gludish. The two are repurposing their HIV discoveries to study how COVID-19 gets transmitted.
Russell and Gludish’s research dials into one key aspect of virus transmission — determining what viral genomes cause disease through the molecular visualization of the spread of infection within human cells.
Viruses depend on the DNA replication machinery of living host organisms to survive. To better understand how viruses cause disease, molecular visualization allows scientists to tag viral DNA with molecules that fluoresce green, identifying how viral genome sequences insert themselves into human genes.
Gludish and Russell’s November paper in Nature announced a novel cell line — cells derived from multicellular organisms, grown in controlled conditions — that allow for analysis of HIV replication using fluorescent genes.
Russell and Gludish hope to ship the fluorescent cell lines designed on the Ithaca campus to South Africa to allow their colleague to culture those cells with gas samples from COVID-19 infected patients to study virus replication.
“[Through this method, we can identify] how many active variants are transmitted by a person over time, under different circumstances,” Russell said. “How long do those variants remain infectious?”
Russell’s lab is now also working toward better understanding the natural history of COVID-19, the progression of disease when left unchecked in the human body, through adapting the HIV cell lines to COVID-19 and to better quantify the threshold necessary for virus transmission from close contact.
Currently, COVID -19 is understood to spread through the spread of respiratory droplets and is picked up in the upper respiratory tract. However, the Centers for Disease Control and Prevention still warns that significant data is missing before scientists will be able to make predictions about how COVID-19 behaves — and Russell’s lab is looking to add to that data.
“We currently have no functional readout to quantify transmission,” Russell said. “We do not know if all the aerosols from a sick patient contain viral genomes and are functionally infectious.”
Their data also has significant implications in molecular drug screening — which pinpoints how the body responds to drug therapies — shifting the understanding of COVID-19 treatment possibilities, according to Russell.
From past experiments on HIV, Russell and Gludish understand the critical insight from studying the natural history of viruses. Their cell line, TZM-gfp, allowed them to find important patterns about the natural history of HIV.
In the past, HIV was thought of as a disease that slowly pierces the primary immune defenses until a person becomes immunocompromised and susceptible to death from infections, according to Russell.
However, the TZM-gfp cell-lines have helped Russell’s lab identify reservoirs of HIV in their patients’ lungs, providing more evidence as to why minor upper respiratory tract infections are deadlier to HIV patients.
Because current medication for HIV targets cells carrying viral genes, using TZM-gfp in the early stages of infection allows for localization and prevention of HIV spread.
According to Russell, the goal is to translate the fluorescent cell line technology used with HIV to identify COVID-19.
This is done through culturing the engineered cells with air samples from infected individuals to identify what conditions support the transmission between individuals and limit this transmission to decrease virus mutations and prevent deadlier variants from arising.