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Scripps Research on page 16
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Scripps Research from page 14 technologies that use two-factor authentication, such as
requiring users to enter a password and then respond to
This work was supported by funding from the U.S. Centers a confirmation email.
for Disease Control and Prevention (75D30121P10258, This two-part mechanism also opens the door to
75D30120C09795), National Institutes of Health vaccination approaches that can exploit the immune cascade
(5T32AI007244-38, 1DP1AT010885, S10OD026929), that is initiated before the virus can start to replicate in the
National Institute of Allergy and Infectious Diseases host cell, after PQBP1 has decorated the molecule.
(3U19AI135995-03S2, U19AI135995, U01AI151812), “While the adaptive immune system has been a main
National Center for Advancing Translational Sciences focus for HIV research and vaccine development, our
(UL1TR002550), the Conrad Prebys Foundation, National discoveries clearly show the critical role the innate
Science Foundation (RAPID 2029069), and the San Diego immune response plays in detecting the virus,” says
County Health and Human Services Agency. For innate immune system activation against HIV-1, Scripps Sunnie Yoh, PhD, first author of the study and senior
Photos by SEARCH Alliance Research scientists have found that the protein PQBP1’s staff scientist in Chanda’s lab. “In modulating the narrow
recognition of incoming HIV-1 particles (depicted in red) window in this two-step process – after PQBP1 has
Immune System Uses Two- is required for cGAS activation, a production of cGAMP decorated the viral capsid, and before the virus is able

Step Verification To Defend (depicted in green), in human dendritic cells. Nuclei (Dapi) to insert itself into the host genome and replicate – there
are depicted in blue.
is the potential to develop novel adjuvanted vaccine
Against HIV The innate immune system is activated before the strategies against HIV-1.”

By shedding light on the workings of the innate
adaptive immune system, which is the body’s secondary immune system, these findings also illuminate how our
Scripps Research discovery could offer new methods line of defense that involves more specialized functions, bodies respond to other autoimmune or neurodegenerative
for treating HIV, while uncovering the innate immune such as generating antibodies. One of the innate immune inflammatory diseases. For example, PQBP1 has been
system’s role in other diseases. system’s primary responsibilities is recognizing between shown to interact with tau – the protein that becomes
Human immunodeficiency virus 1, more commonly “self” (our own proteins and genetic material) and foreign dysregulated in Alzheimer’s disease – and activate the
known as HIV-1, is known for its uncanny ability to evade elements (such as viruses or other pathogens). Cyclic same inflammatory cGAS pathway. The researchers will
the immune system. Scientists at Scripps Research and GMP-AMP synthase (cGAS) is a key signaling protein in continue to investigate how the innate immune system
collaborators have now uncovered how our innate immune the innate immune system that senses DNA floating in a is involved in disease onset and progression, as well as
system – the body’s first line of quick defense in attacking cell. If cGAS does detect a foreign presence, it activates how it distinguishes between self and foreign cells.
foreign invaders – detects HIV-1, even when the virus is a molecular pathway to fight off the invader. In addition to Yoh and Chanda, authors of the study,
present in very small amounts. However, because HIV-1 is an RNA virus, it produces “Recognition of HIV-1 Capsid Licenses Innate Immune
The findings, published on July 8 in Molecular Cell, very little DNA – so little, in fact, that scientists have not Response to Viral Infection,” include Na Rae Ahn and
reveal the two-step molecular strategy that jolts the innate understood how cGAS and the innate immune system are Heather Curry of Scripps Research; João I. Mamede of
immune response into action when exposed to HIV-1. This able to detect it and distinguish it from our own DNA. Northwestern University and Rush University Medical
discovery could impact drug development for HIV treatments Scripps Research scientists discovered that the innate Center; Gianguido C. Cianci, Lacy M. Simons, Judd
and vaccines, as well as shape our understanding of how immune system requires a two-step security check for it to F. Hultquist and Thomas J. Hope of Northwestern
the innate immune response is implicated in other areas – activate against HIV-1. The first step involves an essential University; Derrick Lau, Andrew Tuckwell and Till
including neurodegenerative disorders such as Alzheimer’s. protein – polyglutamine binding protein 1 (PQBP1) – Böcking of the University of New South Wales; Maria T
“This research delineates how the immune system recognizing the HIV-1 outer shell as soon as it enters the cell Sánchez-Aparicio and Adolfo García-Sastre of the Icahn
can recognize a very cryptic virus, and then activate and before it can replicate. PQBP1 then coats and decorates School of Medicine at Mount Sinai; Joshua Temple and
the downstream cascade that leads to immunological the virus, acting as an alert signal to summon cGAS. Once the Yong Xiong of Yale University; Nina V. Fuchs and Renate
activation,” says Sumit Chanda, Ph.D., professor in the viral shell begins to disassemble, cGAS activates additional König of Paul Ehrlich Institute; Stéphanie Gambut of
Department of Immunology and Microbiology. “From immune-related pathways against the virus. Rush University Medical Center; Laura Riva of Calibr;
a therapeutic potential perspective, these findings open The researchers were initially surprised to find that and Xin Yin of the Harbin Veterinary Research Institute.
up new avenues for vaccines and adjuvants that mimic two steps are required for innate immune activation Funding was provided by NIAID of the National
the immune response and offer additional solutions for against HIV-1, as most other DNA-encoding viruses only Institutes of Health, the Gilead Sciences Research Scholars
preventing HIV infection.” activate cGAS in one step. This is a similar concept to Program in HIV and the German Research Foundation.

Brain

Exploration

Day

August 27, 2022 from 10 am to 1 pm

Brain Exploration Day returns to the Max Planck Florida Institute for
Neuroscience from 10 am to 1 pm on August 27, 2022. Help us celebrate
the 10th anniversary of the Institute’s opening with games, prizes, hands-
on stations, tours, and other opportunities to learn about the incredible
brain research taking place right here in South Florida. This fun and free
event is open to all ages, but most activities are best suited for ages 4 and
older.

Advanced registration required. Sign up at mpfi.org/explore or
scan the QR code below. For questions, email info@mpfi.org

Use your phone’s
camera to scan and
learn more!

MAX PLANCK FLORIDA
One Max Planck Way, Jupiter, FL 33458 CELEBRATING 10 YEARS IN THE SOUTH FLORIDA LIFE SCIENCE COMMUNITY
INSTITUTE FOR NEUROSCIENCE