Firefly Gene Helps Light Up the Map of Female HIV Transmission

A recent study has shown that human immunodeficiency virus (HIV) enters cells throughout the entire female reproductive tract (FRT) from the labia to the ovary—not just in the cervix, as previously thought.

Daniel J. Stieh, PhD, Northwestern University, Chicago, Illinois, and colleagues published the results of their study in the journal Cell Host and Microbe.

According to the authors, “[d]eveloping effective prevention measures for HIV is hindered by incomplete knowledge of the phenotype and localization of the initial target cells of infection after mucosal viral exposure.”

It was previously believed that, during heterosexual sex, HIV transmission from men to women occurred through the cervix. However, the difficulty in detecting rare infected cells immediately after mucosal HIV transmission has hindered scientists’ understanding of exactly what cells are initially targeted by the virus.

With this in mind, the researchers conducted an HIV transmission study using the macaque simian immunodeficiency virus (SIV) challenge model. They aimed to investigate the earliest time points after vaginal challenge with SIV, in order to improve understanding of HIV transmission and key target cells.

They inserted the luciferase gene from fireflies into SIV, along with another gene that produces fluorescent proteins, thereby producing a reporter virus. The reporter virus was then combined with the SIV.

This technology allowed the researchers to map out the pathway of the virus in the animal model, because when the modified SIV was introduced to the vaginas of the uninfected macaques, cells fluoresced when they became newly infected with SIV.

According to the authors, the results of this study provided the first evidence that “SIV infection is found throughout the FRT, from the labia to the ovaries, demonstrating that prevention measures must protect the entire organ system to afford maximal protection”.

They also showed that, Th17 cells were the main target of early infection throughout the reproductive tract. These cells represent a small but critical subset of T cells that form the first line of immune defense in the host against invading pathogens. Previous studies have also shown that Th17 cells are lost very early in the course of HIV and SIV infections.

This preferential and early infection of Th17 cells during HIV transmission is unexpected and has important implications. Because Th17 cells are important for maintaining the epithelial integrity of mucosal surfaces in the body, their loss may play a role in the subsequent inflammation that sets off further HIV replication, allowing the virus to spread.

“Preferential infection of cells from the Th17 lineage could explain the known conditions that increase HIV acquisition, including sexually transmitted infections and bacterial vaginosis,” the authors write. Nevertheless, they stress that “[h]ow these conditions precisely influence mucosal barrier function or the density of target cells remains to be determined”.

“This opens new opportunities for interventions to protect these cells and prevent HIV transmission,” the authors conclude.

Dr. Parry graduated from the University of Liverpool, England in 1997 and is a board-certified veterinary pathologist. After 13 years working in academia, she founded Midwest Veterinary Pathology, LLC where she now works as a private consultant. She is passionate about veterinary education and serves on the Indiana Veterinary Medical Association’s Continuing Education Committee. She regularly writes continuing education articles for veterinary organizations and journals, and has also served on the American College of Veterinary Pathologists’ Examination Committee and Education Committee.