Using a newly developed sequencing assay, researchers have pinpointed the specific memory T cells where latent replication-competent HIV ‘hides’ in the human body to evade immune detection. Their paper was published this week in Cell Reports.
When HIV replicates, it tends to make errors and release defective viruses that can't themselves replicate. This can confound study results that seek to quantify the presence of replication-competent HIV hiding out in the body.
To overcome this, a team of scientists at the University of Sydney developed an assay called The Full-Length Individual Proviral Sequencing (FLIPS) assay, which uses NGS to sequence near full-length HIV-1 proviral genomes allowing them to determine replication competency.
With this test, the team was able to determine that 5% of viral genomes were replication-competent and that they preferentially hide out in specific subsets of CD4+ T cells.
"Previously it was thought that HIV was hiding primarily in central memory T-cells, but our new HIV genetic sequencing test has revealed that the majority of replication-competent virus is actually hiding in effector memory T-cells” said Associate Professor Sarah Palmer who was the lead researcher of the study. "HIV is really very clever. Essentially, it is hiding in the exact same cells within the immune system that are meant to attack it."
These findings help explain why ART can stop the virus from replicating, but never fully clear the virus from a person’s system. Future therapies that focus on clearing the virus from these effector memory T-cells may be able to more thoroughly rid the body of HIV.