Research Highlight October 02, 2015

Retroviruses use CD169-mediated trans-infection of permissive lymphocytes to establish infection

Retroviruses are a family of viruses that includes human immunodeficiency virus (HIV) and various animal leukemia viruses. They carry single-stranded RNA that is reverse transcripted to DNA, which is incorporated into the host cell genome then translated and transcribed with the host cell’s own genes. Retroviruses are known to spread between cells in vitro, but mechanisms for spread in vivo are not well understood. Knowledge of how the spread occurs is important for improving HIV prevention and therapies.

To study the spread of retroviruses in vivo, researchers led by Walter Mothes of the Yale University School of Medicine used immunosuppressed (NSG) mice with human immune engraftments, developed by JAX Professor Leonard Shultz. In a paper published online on October 1 in Science, they showed that murine leukemia virus (MLV) and HIV first captured by CD169+ macrophages. CD169 is a cell adhesion molecule found on the surfaces of some macrophages and normally mediates cell-to-cell signaling. It appears that retroviruses are able to utilize the adhesion pathway as an efficient method to infect host cells. Blocking CD169 with antibodies significantly reduced retroviral capture by the macrophages.

The researchers then determined that CD169+ macrophages serve to concentrate viruses and deliver them to B-1 cells—a sub-class of B cell lymphocyte—for infection. The macrophages form long-lived contacts with the B-1 cells, which spreads the infection through a synaptic contact. In lymph nodes, the infected B-1 cells spread the infection through similar cell-to-cell transfers. The researchers plan to test this in vivo model of retroviral spread further to explore its potential for therapeutic intervention.

Science DOI:10.1126/science.aab2749