Benedict Lab

Benedict Lab

"As an immunologist, my hope is that something I am working on is going to make a difference to human health. That’s what interests me – the possibility to combat human disease." — Chris Benedict, Ph.D. // Associate Professor
Center for Infectious Disease


My laboratory studies the strategies that viruses use to escape detection by our immune system, which help them to replicate in our cells and, in some cases, establish lifelong infections that we can never clear. We have a particular interest in those virus-employed tricks that target proteins of the tumor necrosis factor (TNF) family, as these proteins released by our immune cells are fundamentally important in promoting immunity. We have a particular interest in cytomegalovirus (CMV), which is a member of the herpesvirus family similar to ‘mono’ (Epstein-Barr) and the chicken pox (Varicella zoster) viruses. CMV encodes one of the largest viral genomes (~230,000 base pairs), and more than half of it is dedicated to throwing up smoke screens that fool our immune systems, including many that block the TNFs. We believe that studying the very unique CMV strategies that allow it to evade detection by our immune system facilitates fundamental new discoveries about our health. In addition, our lab is focused on finding new ways to combat the diseases that CMV can cause in certain settings. CMV is the No. 1 infectious cause of birth defects in the U.S. today, causing severe disease if immunity is naïve or compromised (e.g. infection of babies in the womb and transplant patients), and we are developing new vaccine strategies to combat this. If you have a healthy immune system, CMV infection is largely benign. However, like the chicken pox that can reemerge 50 years later to cause shingles, CMV ‘hides’ in your body for life and can pop-out again when your immune system is weakened or older. Consequently, CMV is a likely contributor to auto-inflammatory disorders such as vascular disease and immune senescence, and may even contribute to some cancers. One of our recent discoveries could aid efforts to in the development of a CMV vaccine.

From The Lab

Jan 29, 2015 //  Scientific American

Your immune system is made, not born

Mar 13, 2013 // San Diego Union Tribune

Harmful virus might have achilles' heel

Mar 13, 2013

Researchers advance fight against leading infectious cause of congenital birth defects

Benedict Lab


Journal of Virology

Cytomeglaovirus-specific CD4 T cells are cytolytic and mediate vaccine protection

Verma S, Weiskopf D, Gupta A, McDonald B, Peters B, Sette A, Benedict CA
Journal of Immunology

Cardif (MAVS) regulates the maturation of NK cells

Haynes LD, Verma S, McDonald B, Wu R, Tacke R,Nowyhed HN, Ekstein J, Feuvrier A, Benedict CA, Hedrick CC
PLoS Pathogens

Inhibition of the TRAIL death receptor by CMV reveals its importance in NK cell-mediated antiviral defense

Verma S, Loewendorf A, Wang Q, McDonald B, Redwood A, Benedict CA
Cell Host & Microbe

Neutrophils recruited by IL-22 in peripheral tissues function as TRAIL-dependent antiviral effectors against MCMV

Stacey MA, Marsden M, Pham N TA, Clare S, Dolton G, Stack G, Jones E, Klenerman P, Gallimore AM, Taylor PR, Snelgrove…
Journal of Immunology

Distinct requirements of activation of NKT and NK cells during viral infection

Tyznik AJ, Verma S, Wang Q, Kronenberg M, Benedict CA
Expert Review of Vaccines

A CMV vaccine: TREATing despite the TRICKs

Benedict, CA
Journal of Immunology

SD160 activation by herpesvirus entry mediator augments inflammatory cytokine production and cotylytic function by NK cells

Sedy JR, Bjordahl RL, Bekiaris V, Macauley MG, Ware BC, Norris PS, Lurain NS, Benedict CA, Ware CF
Journal of Virology

Lymphoid-tissue stromal cells coordinate innate defense to cytomegalovirus

Verma S, Wang Q, Chodaczek G, Benedict CA
Journal of Virology

CD27-CD70 costimulation controls T cell immunity during acute and persistent cytomegalovirus infection

Welten SP, Redeker A, Franken KL, Benedict CA, Yagira H, Wensveen FM, Borst J, Melief CJ, van Lier RA, van Gisbergen…
Journal of Virology

The myeloid transcription factor GATA-2 regulates the viral UL144 gene during human cytomegalovirus latency in an isolate-specific manner

Poole E, Walther A, Raven K, Benedict CA, Mason GM, Sinclair J
PLoS Pathogens

Structure of human cytomegalovirus UL141 binding to TRAIL-R2 reveals novel, non-canonical death receptor interactions

Nemčovičová I, Benedict CA, Zajonc DM
Cell Host & Microbe

Human cytomegalovirus glycoprotein UL141 targets the TRAIL death receptors to thwart host innate antiviral defenses

Smith W, Tomasec P, Aicheler R, Loewendorf A, Nemčovičová I, Wang EC, Stanton RJ, Macauley M, Norris P, Willen L,…
Nature Reviews Drug Discovery

Clinical targeting of the TNF and TNFR superfamilies

Croft M, Benedict CA, Ware CF
Journal of Experimental Medicine

TRAIL: not just for tumors anymore?

Benedict CA, Ware CF
Viral Immunology

Dissecting the requirements for maintenance of the CMV-specific memory T-cell pool

Loewendorf AI, Arens R, Purton JF, Surth CD, Benedict CA
Journal of Virology

The mouse cytomegalovirus glycoprotein m155 inhibits CD40 expression and restricts CD4 T cell responsesc

Loewendorf AI, Steinbrueck L, Peter C, Busche A, Benedict CA, Kay-Jackson PC
Journal of Immunology

Differential B7-CD28 costimulatory requirements for stable and inflationary mouse cytomegalovirus-specific memory CD8 T cell populations

Arens R, Loewendorf A, Redeker A, Sierro S, Boon L, Klenerman P, Benedict CA, Schoenberger SP
Science Signaling

The specificity of innate immune responses is enforced by repression of interferon response elements by NF-kB p50

Cheng CS, Feldman KE, Lee J, Verma S, Huang DB, Huynh K, Chang M, Ponomarenko JV, Sun SC, Benedict CA, Ghosh G,…
Journal of Interferon and Cytokine Research

Sources and signals regulating type I interferon production: lessons learned from cytomegalovirus

Verma S, Benedict CA
Journal of Virology

B7-mediated costimulation of CD4 T cells constrains cytomegalovirus persistence

Arens R, Loewendorf A, Her MJ, Schneider-Ohrum K, Shellam GR, Janssen E, Ware CF, Schoenberger SP, Benedict CA
J Virol

cGAS-STING signaling regulates initial innate control of cytomegalovirus infection

Lio CJ, McDonald B, Takahashi M, Dhanwani R, Sharma N, Huang J, Pham E, Benedict CA, Sharma S

Principal Investigator


Chris Benedict, Ph.D.

Associate Professor

Dr. Benedict is an Associate Professor in the division of molecular immunology. Dr. Benedict’s research is focused on the role that signaling by TNF-related cytokines play in antiviral defense, and what viruses do in turn to counteract these cytokines.

Dr. Benedict received his B.S. in chemistry from the University of Minnesota in 1992, and his Ph.D. in 1997 from the University of Southern California in the department of biochemistry and molecular biology. Dr. Benedict did his postdoctoral training at LIAI from 1998-2001, was a research scientist from 2001-2005 and was appointed to the faculty as an Associate Professor in 2005.

Lab Members

Raima Gosh

Lab Assistant


Ankan Gupta

Postdoctoral Fellow

In 2003, I completed my Masters in Physiology from the University of Calcutta, India. In 2004, I joined Dr. Sangeeta Bhaskar’s laboratory at the National Institute of Immunology, India and worked as a Research Fellow until 2011. I obtained my PhD in 2012 in Biotechnology from Jamia Hamdard, India. Currently I am doing my postdoctoral research in Dr. Chris Benedict’s laboratory at LJI since 2012.

Research Focus:
My research is primarily focused on understanding the role of CD4 T cell responses in controlling persistent viral infection, and we use mouse cytomegalovirus (MCMV) as a model system. Our lab identified the first MCMV epitope-specific CD4 T cells, and showed that a unique, ‘late-rising’ response directed against an epitope derived from the viral M09 protein (M09133-147) shows very delayed expansion during ‘late persistence’. Using a variety of molecular and cellular techniques, I am investigating whether these ‘late-risers’ play a unique role in resolving viral persistence during natural infection and in a vaccine setting. Another focus has been to investigate whether late-rising CD4 T cells contribute to vascular complications that are associated with CMV infection, perhaps due to their unique chemokine responsiveness.

Career Goals:
Strategic vaccination to combat persistent infections.

Suhan Lee



Bryan McDonald

Research Technician I

I graduated from UCSD in 2014 with a B.S. degree in Human Biology. I worked as an intern at The Scripps Research Institute, and then joined the Benedict lab at LIAI in 2012 as an intern. I was hired full-time as a technician in 2014.

Research Focus:
My research is focused on acute and persistent infections of the herpesvirus, CMV. I am interested in the role of TNF-related apoptosis inducing ligand (TRAIL) in MCMV infections, and in the factors that govern HCMV latency and cell tropism.

Career Goals:
I plan to pursue a career in scientific research focused on identifying targets and treatments for chronic inflammatory diseases.


Rachid El Morabiti

Lab Manager

After completing my master’s degree in pharmacology at VU University in Amsterdam, I immersed myself in the intriguing field of immunology. I moved from Amsterdam to San Diego to pursue a career at LJI in the Benedict Lab. Dr. Benedict hired me as an intern, and following that has given me an opportunity to be his lab manager.

Research Focus:
My main jobs are to manage the day-to-day operations of the group, as well as conduct my own independent research projects. I am responsible for generating the many stocks of wild-type and mutant cytomegalovirus (CMV) that are used for the labs experiments to study this virus both in vitro and in vivo. To assess the specific immune parameters that control infection, I utilize various techniques such as confocal imaging, multi-paramater FACS analysis, ELISA and plaque assays. Furthermore, I maintain and quality-control the breeding colonies of genetically modified mouse strains, an essential component of the labs research. Lastly, I ensure the lab is incompliance with all corporate and government policy procedures related to Good Laboratory Practices.

Career Goals:

I want to continue developing my scientific and business related skill sets in Dr. Benedict’s lab at LJI. I plan to obtain my business and project management certificates which will help me better coordinate projects and cut deals and establish long-standing relationships with premium vendors that service the lab.

Gaëlle Picarda, Ph.D.

Postdoctoral Fellow

I obtained my masters degree in development and control of health products (University of Nantes, France), and then obtained my Ph.D. degree in the field of bone cancer biology (INSERM UMR_957, Nantes, France). My first postdoctoral fellowship focused on studies of dendritic cell biology and virology for 2 years (INSERM UMR_1064, Nantes, France). Since then, I’ve been pursuing my post-doctoral work at the La Jolla Institute for Allergy and Immunology in Chris Benedict’s lab in the field of viral immunity.

Research interest:
My research projects are focused on studying how immune modulatory proteins produced by cytomegalovirus (CMV) target cytokines of the TNF receptor superfamily. This work will provide new insight into how CMV, and other viruses which establish lifelong infections, counteract host immunity, and will also reveal how we can harness these strategies to develop better approaches to combat cancer and auto-immunity.

Shilpi Verma

Visiting Scientist

Benedict Lab

Research Projects

Chris Benedict, Ph.D. and his laboratory are examining the fashion in which viruses work to control and shape the way the immune system responds to them. Specifically, his lab focuses primarily on molecular antiviral signaling pathways initiated by cytokines of the tumor necrosis factor (TNF) and interferon (IFN) families. Using both cell culture and in vivo models, Benedict's lab studies several different viruses including herpesvirus, influenza and adenovirus.

CMV interfaces with the TRAIL cytokine system

We have recently discovered a novel connection between the TNF-related apoptosis inducing ligand (TRAIL) cytokine system and CMV. TRAIL is a TNF-family cytokine that can bind to several receptors (TRAIL receptor- 1, 2 ,3 and 4), of which two (R1 and R2) encode a cytoplasmic "death domain" and can mediate apoptosis of transformed cells (death receptors, DR). We showed several years ago that human adenovirus encodes 3 proteins in the E3 region of its genome (10.4K/14.5K/6.7K) that specifically downregulate the TRAIL DRs from surface of infected cells, desensitizing them to TRAIL-mediated killing. Now, we have discovered that human CMV (HCMV) also inhibits expression of the TRAIL DRs, and uses the UL141 protein to accomplish this task. In turn, we have solved the three dimensional structure of the UL141/TRAIL-R2 complex by X-ray crystallography in collaboration with Dr. Zajonc’s group at LJI. More recently we have shown that mouse CMV (MCMV) also uses a specific strategy to inhibit the TRAIL-DR via use of m166, the first identified role for this viral protein. In the absence of m166, MCMV replication is highly compromised due to it’s inability to inhibit TRAIL signaling, showing the key importance viral inhibition of this immune pathway plays.

T cell immunity and CMV

HCMV-specific CD8 T cells protect bone marrow transplant patients when used in cellular immunotherapy, and their long-term maintenance is enhanced by CD4 T cells. Importantly, a robust HCMV-specific CD4 T cell response strongly correlates with protection against congenital infection and fewer rejections in kidney transplant patients. In mice, CD4 T cells are absolutely required for controlling persistent MCMV replication in the salivary gland (SG), the main site where the virus replicates for months and is horizontally transmitted, and CD8 T cells provide no control in this organ. We were the first to identify MCMV epitope-specific CD4T cells that arise in several different genetic strains of mice, and are studying the potential of these cells to mediate vaccine protection. We have shown that cosignaling by several key immune pathways (e.g. B7-CD28, PDL1-PD1, OX40-OX40L, 41BB-41BBL) regulates the development and function of MCMV-specific T cells. In turn, viral inhibition of B7-CD28 and CD40-CD40L signaling helps the virus to establish persistent infection and blunt the antiviral CD4 T cell response. We believe that our studies of the mechanism(s) by which the diverse CMV-specific CD4 T cell response is generated will help elucidate how persistent infection is controlled and provide novel insight for vaccine development.

CMV targets the immune checkpoint inhibitor BTLA

Virulent isolates of CMV encode the ul144 orf, and we identified UL144 as an orthologue of the herpesvirus entry mediator (HVEM), a member of the TNF receptor superfamily. When the immune checkpoint inhibitor B and T lymphocyte attenuator (BTLA) was identified as a ligand for HVEM, we showed that UL144 was a specific binding partner for BTLA, and not the other known HVEM ligands LIGHT, LTa and CD160. Strikingly, UL144 inhibits the activation of human T cells to a much greater degree than does HVEM, highlighting how CMV has evolved novel ways to inhibit antiviral immune responses. We have recently shown that UL144 is expressed in myeloid cells latently infected with HCMV, strongly suggesting that this viral protein plays a key role in promoting persistence of this virus in humans. In addition, UL144 can suppress the function of human natural killer (NK) cells by binding to BTLA. Further studies regarding the functional consequences of the UL144-BTLA interaction, both during lytic and latent infection, are a topic of current interest for our lab.

The lymphotoxin-Interferon antiviral immunity axis

Over the last 15 years our lab has been studying the link between lymphotoxins (LT) and the regulation of type I interferons (IFN-I) during CMV infection. Mice deficient in LT signaling pathways show increased susceptibility to infection with MCMV due to their inability to mount a strong, initial IFN-I response to infection. Triggering signaling by the LTß-receptor at the earliest times of CMV infection can restore IFN-I production and protect mice against MCMV infection, highlighting this pathway as critical for innate antiviral defense. We have shown that this LT-IFN axis is operable in stromal cells located in the splenic marginal zone (MZ), and that these MZ stromal cells make copious amounts of IFN-I, similar to the levels produced plasmacytoid dendritic cells (pDC). In addition, it is the this stromal-derived IFN-I that is critical for controlling replication of MCMV at the earliest times of infection, not that produced by pDC and other DC subsets. Signaling by LTß can also dramatically increase production of IFN-I in HCMV infected cells, indicating a conserved importance of this cytokine "axis" in the regulation of CMV pathogenesis.