Category: News

A new paper co-authored by three WaNPRC researchers in Frontiers in Immunology indicates that people with HIV may be at greater risk for prolonged Zika virus (ZIKV) infections, and that people vulnerable to mosquito-borne illnesses like Zika would benefit from protections like vaccines. 

The paper, “Persistent innate immune dysfunction and ZIKV replication in the gastrointestinal tract during SIV infection in pigtail macaques,” suggests that people living with HIV may be at greater risk for prolonged Zika virus infections and that the virus stayed in the body longer. 

Dr. Megan O’Connor, Director Deb Fuller and former WaNPRC researcher and current affiliate Dr. Michael Gale contributed to the paper. The study looked at nonhuman primates (NHPs) co-infected with simian immunodeficiency virus (SIV) and Zika, the disease involved in a well-known outbreak in the Americas in 2015-2016 that infected tens of thousands of people and caused symptoms ranging from a rash and fever to microencephaly in babies (an abnormally small head), and even death. In the study NHPs had a harder time fighting off Zika, and the Zika virus stayed in their body longer, especially in places like the gut.  

They wrote: “Collectively, these findings uniquely suggest that untreated SIV infection may promote inflammatory cellular innate responses and create a state of persistent immune activation that contributes to prolonged ZIKV viremia and persistence in the gastrointestinal tract. Furthermore, these results suggest that people living with HIV and other immunocompromised individuals could be at higher risk for prolonged ZIKV infection, potentially extending the window of ZIKV transmission. These insights highlight the importance of including people living with HIV in strategies for deploying vaccines and treatments against ZIKV.” 

In other words, this indicates that people living with HIV, who have weaker immune systems, might have a harder time fighting off Zika, and it could stay in their bodies for a longer time. The researchers said this means public health officials need to make sure such people get treatments, such as vaccines, to help them fight off Zika more effectively. 

You can read the entire paper, here. 

Dr. Fuller was appointed director of WaNPRC in late last year. 

Dr O’Connor was appointed in February to the University of Washington faculty as Assistant Professor in the Department of Laboratory Medicine and Pathology.  She is a Core Scientist in the WaNPRC Infectious Disease and Translational Medicine Unit and focuses on HIV viral co-infections with the goal of improving treatment and vaccine strategies for people living with HIV and other immunocompromised people.

Chlamydia is one of the most widespread infectious diseases in the world, and it is remarkably difficult to prevent its spread.  However, Dr. Kevin Hybiske, microbiologist and professor at the University of Washington in infectious diseases, microbiology and global health, offers new hope in collaboration with the Washington National Primate Research Center.

In his lab, Dr. Hybiske is unraveling the complex ways this pathogen manipulates human cells to spread and evade the immune system. By understanding these mechanisms, his team aims to develop innovative therapies that could one day lead to better treatments and, ultimately, a reduction in the global health burden caused by this disease.

“Anecdotally, it’s probably one of the oldest bacterial pathogens of multicellular hosts,” Dr Hybiske said. “We study it because we still don’t understand the processes it uses to infect cells (and thus people), and we need to better understand that to so we can improve our ability to treat it.”

According to the World Health Organization, there were more than 128 million new cases of this sexually transmitted infection (STI) in 2020.  And before COVID, it was the most reported infection in the United States.

While Chlamydia can be easily treated with antibiotics, there is no preventative vaccine, and people infected with it often have no symptoms. These factors contribute to the high prevalence of Chlamydia in the population, disproportionally affecting women and people with limited access to medical screenings or treatment. If left undiagnosed and untreated, chlamydia can cause serious problems, including pelvic inflammatory disease and an increased risk of infertility and ectopic pregnancy.

Dr Hybiske’s lab is interested in studying the key steps involved with the development of the disease, in part, by creating “mutants” of chlamydia to learn how one mutant does its job of entering and exiting cells so that it can propagate.

“A big part of my lab is in the business of making Chlamydia mutants,” he said.  “We’re among the best in the world at that. We use this strategy to figure out what’s important” in the ways chlamydia infects and impacts humans.

“Microbiologists make mutants and figure out what processes they can no longer do and trace the facts to a gene that’s been disrupted. And that’s how you figure out how a pathogen does what it needs to do. Whether divide, or attach, or kill a host cell,” he said.  “Until about 10 years ago people who studied chlamydia couldn’t do that.”

A major hurdle to studying this pathogen is that, unlike some other bacteria, chlamydia requires a mammalian host and cannot be grown in a dish. Which is where WaNPRC comes in.

“I have had long professional relationships with investigators at UW who had established the chlamydia infection model in macaques. They’re the best in the world at it,” he said.

“This research is the kind of thing that can only be done in the circumstances that exist at WaNPRC because of the combination of collaborators, and the teams who care for the monkeys,” he said.  “This is the basic science we’ve only recently been able to do, and we’re among the best. We have small libraries of mutants that no one else has, and which we are eagerly hoping to test in relevant models. Our partnership with the WaNPRC allow us to experiment and test in ways that’s never been done.”

Hybiske and his team are keenly aware of the ethical considerations surrounding primate research and take steps to ensure that their work is responsible and beneficial. In a recent pilot study, Hybiske explored the vaccine potential of a new genetically attenuated mutant of Chlamydia and found that exposing monkeys to this vaccine strain was safe and led to immunity against challenge with a pathogenic Chlamydia strain. This type of responsible research is respectful of animal well-being and health and also has the potential to lead to promising advances for addressing human Chlamydia infections. He hopes to receive a grant to pursue this vaccine development further.

The World Health Organization is working to reduce the global burden of sexually transmitted infections like chlamydia, aiming for a 50% reduction in new cases of chlamydia by 2030. “My work slides into that,” Hybiske said.  “I am not someone who normally thinks about vaccine design, my work has mostly been focused on figuring out Chlamydia’s deep molecular secrets.”  And the secret could be connected to creating a mutant of chlamydia with special properties that could be beneficial in a vaccine.

“There’s a well-trod path to vaccine development, and we are at the beginning,” he said. “We’re doing the necessary next steps to see what happens. See where that takes it. Even if this strain doesn’t become a vaccine home run, we are poised to learn a great deal about the primate’s immune response to a Chlamydia vaccine, and this will certainly aid other people who are trying to make vaccines. If we are lucky, one of these vaccine candidates will work great and have an impact on public health.”

As we move deeper into fall and the hours of daylight dwindle, a trio of researchers from the same family has worked together to create new technology that helps humans improve our health and our moods by managing our circadian rhythms. And they say we can thank research monkeys for it. 

In new research from professors Jay and Maureen Neitz of the UW Department of Ophthalmology, and their youngest daughter Alex (who was a graduate research assistant at UW and is now a postdoctoral researcher at the University of California San Diego) helped show that, an LED light that emits alternating wavelengths of orange and blue light helped boost melatonin levels in a group of study participants, shifting their “internal clocks” to align how our body’s supposed to act during different times of day. 

The findings, published in the Journal of Biological Rhythms, show that the alternating wavelengths can influence circadian rhythms, an effective approach to counteract seasonal affective disorder (SAD), among other maladies. 

A host of health and mood problems are attributed to out-of-sync circadian rhythms, Jay Neitz says. The result is “social jet lag” that occurs during seasonal changes and a lack of exposure to natural light, not to mention night jobs and international travel. 

“In extreme cases what this being not synchronized has been linked to diabetes and cancer and all sorts of problems,” he said. “At the very least, people just aren’t at their best. They don’t feel great because their internal clock isn’t set right.  Theirs’s huge interest in this kind of thing.” 

The Neitzes designed an experiment using light that alternated between short- and long-wavelength components that advanced the circadian phase by an average of almost an hour and a half.  

And it’s led to the development of products that produce these alternating blue/orange wavelengths. Called “TUO Circadian Smart Products,” the line consists of an LED lightbulb and various lamps, which can be managed by a smartphone app. 

All this from the trio who mesh work and life and always have.

“There’s a lot of talk about work life balance,” said Jay.  “Our work and lives have just been one thing. We work all the time, and we have two daughters. Our younger daughter, Alex, started working in our lab as a child.”

“It wasn’t like this started in grad school it was a gradual process,” Alex said.  “In grad school I was interested in circadian rhythms, and I went to grad school immediately after undergrad.”  

Like mother, like daughter. Maureen and Alex are both molecular biologists who wound up interested in studying vision and the nonhuman primate model.

Jay credits NHP research stemming from a grant that helped Maureen obtain an electron microscope that enabled researchers to build a complete look at the retina that was the foundation for research that led to the Tho light. So none of it would have happened without NHP research. 

“There are things about the way our eyes work and how they communicate with the central parts of our brain that are unique to primates,” Jay said, recalling contributions of WaNPRC’s Tissue Distribution Program.  “Because of that we got preservation of microdetails of all cells in the retina that could never be gotten from a human.  We believe what we’re seeing in the NHP model is exactly like what happens in a human. There’s just no other example like this.”