Immunology and Infectious Disease Commons^™

Differences In Rhodococcus Equi Infections Based On Immune Status And Antibiotic Susceptibility Of Clinical Isolates In A Case Series Of 12 Patients And Cases In The Literature, Praveen Gundelly, Yasuhiro Suzuki, Julie A. Ribes, Alice C. Thornton

Internal Medicine Faculty Publications

Rhodococcus equi is an unusual zoonotic pathogen that can cause life-threatening diseases in susceptible hosts. Twelve patients with R. equi infection in Kentucky were compared to 137 cases reported in the literature. Although lungs were the primary sites of infection in immunocompromised patients, extrapulmonary involvement only was more common in immunocompetent patients (P > 0.0001). Mortality in R. equi-infected HIV patients was lower in the HAART era (8%) than in pre-HAART era (56%) (P > 0.0001), suggesting that HAART improves prognosis in these patients. Most (85–100%) of clinical isolates were susceptible to vancomycin, clarithromycin, rifampin, aminoglycosides, ciprofloxacin, and imipenem. …

Workplace Safety Concerns Among Co-Workers Of Responder Returning From Ebola-Affected Country, Benjamin P. Chan, Elizabeth R. Daly, Elizabeth A. Talbot

Dartmouth Scholarship

We surveyed public health co-workers regarding attitudes toward a physician who returned to New Hampshire after volunteering in the West African Ebola outbreak. An unexpectedly large (18.0%) proportion of staff expressed discomfort with the Ebola responder returning to work. Employers should take proactive steps to address employee fears and concerns.

Alcohol And Hcv: Implications For Liver Cancer, Gyongyi Szabo, Banishree Saha, Terence Bukong

Gyongyi Szabo

Liver cancers are one of the deadliest known malignancies which are increasingly becoming a major public health problem in both developed and developing countries. Overwhelming evidence suggests a strong role of infection with hepatitis B and C virus (HBV and HCV), alcohol abuse, as well as metabolic diseases such as obesity and diabetes either individually or synergistically to cause or exacerbate the development of liver cancers. Although numerous etiologic mechanisms for liver cancer development have been advanced and well characterized, the lack of definite curative treatments means that gaps in knowledge still exist in identifying key molecular mechanisms and pathways …

The Genetics Of Hepatitis C Virus Underlie Its Ability To Escape Humoral Immunity, Jay Kolls, Gyongyi Szabo

Gyongyi Szabo

Hepatitis C virus (HCV) is a leading cause of chronic liver disease, and efforts to develop therapeutic vaccine strategies have been limited by immune escape due to HCV variants that are resistant to current vaccines or HCV variants that rapidly acquire new resistance-conferring mutations. Recently, the crystal structure of the viral envelope protein E2 region was resolved as well as how E2 docks to the host CD81 protein; therefore, antibodies that block this interaction should prevent viral entry into host cells. In this issue of the JCI, Bailey and colleagues show that immune escape of HCV can occur by naturally …

Repeated Plasmodium Vivax Malaria Relapses In A Peruvian Sailor., Adam P. Mcfarland, Juan F Sanchez, Alejandro Mercado, Julio A Ventocilla, Sofia Cavalcanti, Sofia Gonzalez, Andres G Lescano

Medicine Faculty Publications

Two Plasmodium vivax recurrences in a Peruvian sailor with weight above the 60 kg (cap for primaquine dosage) highlight the importance of adequate radical cure weight dosage for patient treatment and control efforts, particularly within the military.

Dual Engagement Of The Nlrp3 And Aim2 Inflammasomes By Plasmodium-Derived Hemozoin And Dna During Malaria, Parisa Kalantari, Rosane B. Deoliveira, Jennie Chan, Yolanda Corbett, Vijay A. K. Rathinam, Andrea Stutz, Eicke Latz, Ricardo T. Gazzinelli, Douglas T. Golenbock, Katherine A. Fitzgerald

Katherine A. Fitzgerald

Hemozoin (Hz) is the crystalline detoxification product of hemoglobin in Plasmodium-infected erythrocytes. We previously proposed that Hz can carry plasmodial DNA into a subcellular compartment that is accessible to Toll-like receptor 9 (TLR9), inducing an inflammatory signal. Hz also activates the NLRP3 inflammasome in primed cells. We found that Hz appears to colocalize with DNA in infected erythrocytes, even before RBC rupture or phagolysosomal digestion. Using synthetic Hz coated in vitro with plasmodial genomic DNA (gDNA) or CpG oligodeoxynucleotides, we observed that DNA-complexed Hz induced TLR9 translocation, providing a priming and an activation signal for inflammasomes. After phagocytosis, Hz and …

Another Armed Cd4(+) T Cell Ready To Battle Hepatocellular Carcinoma, Roniel Cabrera, Gyongyi Szabo

Gyongyi Szabo

No abstract provided.

Human Ezrin-Moesin-Radixin Proteins Modulate Hepatitis C Virus Infection, Terence Bukong, Karen Kodys, Gyongyi Szabo

Gyongyi Szabo

Host cytoskeletal proteins of the ezrin-moesin-radixin (EMR) family have been shown to modulate single-stranded RNA virus infection through regulating stable microtubule formation. Antibody engagement of CD81, a key receptor for hepatitis C virus (HCV) entry, induces ezrin phosphorylation. Here we tested the role of EMR proteins in regulating HCV infection and explored potential therapeutic targets. We show that HCV E2 protein induces rapid ezrin phosphorylation and its cellular redistribution with F-actin by way of spleen tyrosine kinase (SYK). Therapeutically blocking the functional roles of SYK or F-actin reorganization significantly reduced Huh7.5 cell susceptibility to HCV J6/JFH-1 infection. Using gene regulation, …

Differences In Innate Immune Signaling Between Alcoholic And Non-Alcoholic Steatohepatitis, Jan Petrasek, Timea Csak, Michal Ganz, Gyongyi Szabo

Gyongyi Szabo

The similar histopathological characteristics of alcoholic steatohepatitis (ASH) and non-alcoholic steatohepatitis (NASH), and the crucial role of the innate immune response in both conditions may lead to the assumption that ASH and NASH represent the same pathophysiological entities caused by different risk factors. In this review paper, we elaborate on the pathophysiological differences between these two entities and highlight the disease-specific involvement of signaling molecules downstream of the Toll-like receptor 4, and the differential mechanism by which the inflammasome contributes to ASH versus NASH. Our findings emphasize that ASH and NASH have disease-specific mechanisms and therefore represent distinct biological entities. …

Human Type 2 Myeloid Dendritic Cells Produce Interferon-Lambda And Amplify Interferon-Alpha In Response To Hepatitis C Virus Infection, Shuye Zhang, Karen Kodys, Kui Li, Gyongyi Szabo

Gyongyi Szabo

BACKGROUND and AIMS: The type III interferons (IFN-lambdas: interleukin [IL]-28a, IL-28b, and IL-29) have important roles in hepatitis C virus (HCV) infection, but little is understood about what cells produce these cytokines or how production is activated. We investigated whether human immune cells recognize HCV-infected cells and respond by producing IFN-lambda. METHODS: We cultured healthy human peripheral blood mononuclear cells (PBMCs) with different populations of immune cells and Japanese fulminant hepatitis-1 (JFH-1) HCV-infected Huh7.5 (cell culture-derived HCV particles [HCVcc]/Huh7.5) cells. RESULTS: Human PBMCs recognized HCVcc/Huh7.5 cells and responded by producing IFN-alpha, IFN-gamma, and IFN-lambda. A rare subset of myeloid dendritic …

Toll-Like Receptors In Liver Disease, Jan Petrasek, Timea Csak, Gyongyi Szabo

Gyongyi Szabo

Activation of inflammatory signaling pathways is of central importance in the pathogenesis of alcoholic liver disease (ALD) and nonalcoholic steatohepatitis (NASH). Recent studies demonstrated that Toll-like receptors, the sensors of microbial and endogenous danger signals, are expressed and activated in innate immune cells as well as in parenchymal cells in the liver and thereby contribute to ALD and NASH. In this review, we emphasize the importance of gut-derived endotoxin and its recognition by TLR4 in the liver. The significance of TLR-induced intracellular signaling pathways and cytokine production as well as the contribution of individual cell types to the inflammation is …

Dengue: Defining Protective Versus Pathologic Immunity, Alan Rothman

Alan Rothman

Dengue is an expanding public health problem, and an effective vaccine remains elusive. This review discusses how the significant influence of sequential infection with different dengue virus serotypes on the severity of disease can be viewed in terms of beneficial and detrimental effects of heterologous immunity. A more complete understanding of these effects is likely to be critical for predicting optimal vaccine-induced immune responses.

Dengue Virus Nonstructural Protein Ns5 Induces Interleukin-8 Transcription And Secretion, Carey L. Medin, Katherine A. Fitzgerald, Alan L. Rothman

Alan Rothman

Elevated circulating levels of chemokines have been reported in patients with dengue fever and are proposed to contribute to the pathogenesis of dengue disease. To establish in vitro models for chemokine induction by dengue 2 virus (DEN2V), we studied a variety of human cell lines and primary cells. DEN2V infection of HepG2 and primary dendritic cells induced the production of interleukin-8 (IL-8), RANTES, MIP-1alpha, and MIP-1beta, whereas only IL-8 and RANTES were induced following dengue virus infection of HEK293 cells. Chemokine secretion was accompanied by an increase in steady-state mRNA levels. No chemokine induction was observed in HEK293 cells treated …

T Cell Receptor Vbeta Gene Usage In Thai Children With Dengue Virus Infection, Susan Gagnon, Anita Leporati, Sharone Green, Siripen Kalayanarooj, David Vaughn, Henry Stephens, Saroj Suntayakorn, Ichiro Kurane, Francis Ennis, Alan Rothman

Alan Rothman

T lymphocyte activation during dengue is thought to contribute to the pathogenesis of dengue hemorrhagic fever (DHF). We examined the T cell receptor Vbeta gene usage by a reverse transcriptase-polymerase chain reaction assay during infection and after recovery in 13 children with DHF and 13 children with dengue fever (DF). There was no deletion of specific Vbeta gene families. We detected significant expansions in usage of single Vbeta families in six subjects with DHF and three subjects with DF over the course of infection, but these did not show an association with clinical diagnosis, viral serotype, or HLA alleles. Differences …

Quantitation Of Cd8+ T Cell Responses To Newly Identified Hla-A*0201-Restricted T Cell Epitopes Conserved Among Vaccinia And Variola (Smallpox) Viruses, Masanori Terajima, John Cruz, Gregory Raines, Elizabeth Kilpatrick, Jeffrey Kennedy, Alan Rothman, Francis Ennis

Alan Rothman

Immunization with vaccinia virus resulted in long-lasting protection against smallpox and was the approach used to eliminate natural smallpox infections worldwide. Due to the concern about the potential use of smallpox virus as a bioweapon, smallpox vaccination is currently being reintroduced. Severe complications from vaccination were associated with congenital or acquired T cell deficiencies, but not with congenital agammaglobulinemia, suggesting the importance of T cell immunity in recovery from infection. In this report, we identified two CD8+ T cell epitopes restricted by the most common human major histocompatibility complex (MHC) class I allele, HLA-A*0201. Both epitopes are highly conserved in …

Human Treg Responses Allow Sustained Recombinant Adeno-Associated Virus-Mediated Transgene Expression, Christian Mueller, Jeffrey Chulay, Bruce Trapnell, Margaret Humphries, Brenna Carey, Robert Sandhaus, Noel Mcelvaney, Louis Messina, Qiushi Tang, Farshid Rouhani, Martha Campbell-Thompson, Ann Fu, Anthony Yachnis, David Knop, Guo-Jie Ye, Mark Brantly, Roberto Calcedo, Suryanarayan Somanathan, Lee Richman, Robert Vonderheide, Maigan Hulme, Todd Brusko, James Wilson, Terence Flotte

Christian Mueller

Recombinant adeno-associated virus (rAAV) vectors have shown promise for the treatment of several diseases; however, immune-mediated elimination of transduced cells has been suggested to limit and account for a loss of efficacy. To determine whether rAAV vector expression can persist long term, we administered rAAV vectors expressing normal, M-type alpha-1 antitrypsin (M-AAT) to AAT-deficient subjects at various doses by multiple i.m. injections. M-specific AAT expression was observed in all subjects in a dose-dependent manner and was sustained for more than 1 year in the absence of immune suppression. Muscle biopsies at 1 year had sustained AAT expression and a reduction …

T Cell Receptor Vbeta Gene Usage In Thai Children With Dengue Virus Infection, Susan J. Gagnon, Anita M. Leporati, Sharone Green, Siripen Kalayanarooj, David W. Vaughn, Henry A. F. Stephens, Saroj Suntayakorn, Ichiro Kurane, Francis A. Ennis, Alan L. Rothman

Sharone Green

T lymphocyte activation during dengue is thought to contribute to the pathogenesis of dengue hemorrhagic fever (DHF). We examined the T cell receptor Vbeta gene usage by a reverse transcriptase-polymerase chain reaction assay during infection and after recovery in 13 children with DHF and 13 children with dengue fever (DF). There was no deletion of specific Vbeta gene families. We detected significant expansions in usage of single Vbeta families in six subjects with DHF and three subjects with DF over the course of infection, but these did not show an association with clinical diagnosis, viral serotype, or HLA alleles. Differences …

Prediction Of Dengue Disease Severity Among Pediatric Thai Patients Using Early Clinical Laboratory Indicators, James A. Potts, Robert V. Gibbons, Alan L. Rothman, Anon Srikiatkhachorn, Stephen J. Thomas, Pra-On Supradish, Stephenie C. Lemon, Daniel H. Libraty, Sharone Green, Siripen Kalayanarooj

Sharone Green

BACKGROUND: Dengue virus is endemic in tropical and sub-tropical resource-poor countries. Dengue illness can range from a nonspecific febrile illness to a severe disease, Dengue Shock Syndrome (DSS), in which patients develop circulatory failure. Earlier diagnosis of severe dengue illnesses would have a substantial impact on the allocation of health resources in endemic countries. METHODS AND FINDINGS: We compared clinical laboratory findings collected within 72 hours of fever onset from a prospective cohort children presenting to one of two hospitals (one urban and one rural) in Thailand. Classification and regression tree analysis was used to develop diagnostic algorithms using different …

Treatment With Monoclonal Antibodies Against Clostridium Difficile Toxins, Israel Lowy, Deborah Molrine, Brett Leav, Barbara Blair, Roger Baxter, Dale Gerding, Geoffrey Nichol, William Thomas, Mark Leney, Susan Sloan, Catherine Hay, Donna Ambrosino

William D Thomas Jr

BACKGROUND: New therapies are needed to manage the increasing incidence, severity, and high rate of recurrence of Clostridium difficile infection.

METHODS: We performed a randomized, double-blind, placebo-controlled study of two neutralizing, fully human monoclonal antibodies against C. difficile toxins A (CDA1) and B (CDB1). The antibodies were administered together as a single infusion, each at a dose of 10 mg per kilogram of body weight, in patients with symptomatic C. difficile infection who were receiving either metronidazole or vancomycin. The primary outcome was laboratory-documented recurrence of infection during the 84 days after the administration of monoclonal antibodies or placebo.

RESULTS: …

Structural And Thermodynamic Basis Of Amprenavir/Darunavir And Atazanavir Resistance In Hiv-1 Protease With Mutations At Residue 50, Seema Mittal, Rajintha Bandaranayake, Nancy King, Moses Prabu-Jeyabalan, Madhavi Nalam, Ellen Nalivaika, Nese Yilmaz, Celia Schiffer

Celia A. Schiffer

Drug resistance occurs through a series of subtle changes that maintain substrate recognition but no longer permit inhibitor binding. In HIV-1 protease, mutations at I50 are associated with such subtle changes that confer differential resistance to specific inhibitors. Residue I50 is located at the protease flap tips, closing the active site upon ligand binding. Under selective drug pressure, I50V/L substitutions emerge in patients, compromising drug susceptibility and leading to treatment failure. The I50V substitution is often associated with amprenavir (APV) and darunavir (DRV) resistance, while the I50L substitution is observed in patients failing atazanavir (ATV) therapy. To explain how APV, …

Serine/Threonine Acetylation Of Tgfbeta-Activated Kinase (Tak1) By Yersinia Pestis Yopj Inhibits Innate Immune Signaling, Nicholas Paul Paquette, Joseph E. Conlon, Charles R. Sweet, Florentina Rus, Lindsay Wilson, Andrea J. Pereira, Charles V. Rosadini, Nadege Goutagny, Alexander N. R. Weber, William S. Lane, Scott A. Shaffer, Stephanie Maniatis, Katherine A. Fitzgerald, Lynda M. Stuart, Neal S. Silverman

Katherine A. Fitzgerald

The Gram-negative bacteria Yersinia pestis, causative agent of plague, is extremely virulent. One mechanism contributing to Y. pestis virulence is the presence of a type-three secretion system, which injects effector proteins, Yops, directly into immune cells of the infected host. One of these Yop proteins, YopJ, is proapoptotic and inhibits mammalian NF-kappaB and MAP-kinase signal transduction pathways. Although the molecular mechanism remained elusive for some time, recent work has shown that YopJ acts as a serine/threonine acetyl-transferase targeting MAP2 kinases. Using Drosophila as a model system, we find that YopJ inhibits one innate immune NF-kappaB signaling pathway (IMD) but not …

Serine/Threonine Acetylation Of Tgfbeta-Activated Kinase (Tak1) By Yersinia Pestis Yopj Inhibits Innate Immune Signaling, Nicholas Paul Paquette, Joseph E. Conlon, Charles R. Sweet, Florentina Rus, Lindsay Wilson, Andrea J. Pereira, Charles V. Rosadini, Nadege Goutagny, Alexander N. R. Weber, William S. Lane, Scott A. Shaffer, Stephanie Maniatis, Katherine A. Fitzgerald, Lynda M. Stuart, Neal S. Silverman

Neal Silverman

The Gram-negative bacteria Yersinia pestis, causative agent of plague, is extremely virulent. One mechanism contributing to Y. pestis virulence is the presence of a type-three secretion system, which injects effector proteins, Yops, directly into immune cells of the infected host. One of these Yop proteins, YopJ, is proapoptotic and inhibits mammalian NF-kappaB and MAP-kinase signal transduction pathways. Although the molecular mechanism remained elusive for some time, recent work has shown that YopJ acts as a serine/threonine acetyl-transferase targeting MAP2 kinases. Using Drosophila as a model system, we find that YopJ inhibits one innate immune NF-kappaB signaling pathway (IMD) but not …

Persistence Of Episomal Hiv-1 Infection Intermediates In Patients On Highly Active Anti-Retroviral Therapy, Mark Sharkey, Ian Teo, Thomas Greenough, Natalia Sharova, Katherine Luzuriaga, John Sullivan, R. Bucy, Leondios Kostrikis, Ashley Haase, Claire Veryard, Raul Davaro, Sarah Cheeseman, Jennifer Daly, Carol Bova, Richard Ellison, Brian Mady, Kwan Lai, Graeme Moyle, Mark Nelson, Brian Gazzard, Sunil Shaunak, Mario Stevenson

Associate Professor Mark Nelson

Treatment of HIV-1-infected individuals with a combination of anti-retroviral agents results in sustained suppression of HIV-1 replication, as evidenced by a reduction in plasma viral RNA to levels below the limit of detection of available assays. However, even in patients whose plasma viral RNA levels have been suppressed to below detectable levels for up to 30 months, replication-competent virus can routinely be recovered from patient peripheral blood mononuclear cells and from semen. A reservoir of latently infected cells established early in infection may be involved in the maintenance of viral persistence despite highly active anti-retroviral therapy. However, whether virus replication …

Immunological Mechanisms Of Extracorporeal Photopheresis In Cutaneous T Cell Lymphoma And Graft Versus Host Disease, Lisa Shiue

Dissertations & Theses (Open Access)

IMMUNOLOGICAL MECHANISMS OF EXTRACORPOREAL PHOTOPHERESIS IN CUTANEOUS T CELL LYMPHOMA AND GRAFT VERSUS HOST DISEASE

Publication No.___________

Lisa Harn-Ging Shiue, B.S.

Supervisory Professor: Madeleine Duvic, M.D.

Extracorporeal photopheresis (ECP) is an effective, low-risk immunomodulating therapy for leukemic cutaneous T cell lymphoma (L-CTCL) and graft versus host disease (GVHD), but whether the mechanism(s) of action in these two diseases is (are) identical or different is unclear. To determine the effects of ECP in vivo, we studied regulatory T cells (T-regs), cytotoxic T lymphocytes (CTLs), and dendritic cells (DCs) by immunofluorescence flow cytometry in 18 L-CTCL and 11 GVHD patients before …

Dendritic Cells In Hepatitis C Infection: Can They (Help) Win The Battle, Angela Dolganiuc, Gyongyi Szabo

Gyongyi Szabo

Infection with hepatitis C virus (HCV) is a public health problem; it establishes a chronic course in ~85% of infected patients and increases their risk for developing liver cirrhosis, hepatocellular carcinoma, and significant extrahepatic manifestations. The mechanisms of HCV persistence remain elusive and are largely related to inefficient clearance of the virus by the host immune system. Dendritic cells (DCs) are the most efficient inducers of immune responses; they are capable of triggering productive immunity and maintaining the state of tolerance to self- and non-self antigens. During the past decade, multiple research groups have focused on DCs, in hopes of …

Hypoxia And Hypoxia Inducible Factors: Diverse Roles In Liver Diseases, Bharath Nath, Gyongyi Szabo

Gyongyi Szabo

Hypoxia has been shown to have a role in the pathogenesis of several forms of liver disease. The hypoxia inducible factors (HIFs) are a family of evolutionarily conserved transcriptional regulators that affect a homeostatic response to low oxygen tension and have been identified as key mediators of angiogenesis, inflammation, and metabolism. In this review we summarize the evidence for a role of HIFs across a range of hepatic pathophysiology. We describe regulation of the HIFs and review investigations that demonstrate a role for HIFs in the development of liver fibrosis, activation of innate immune pathways, hepatocellular carcinoma, as well as …

Mitochondrial Antiviral Signaling Protein Defect Links Impaired Antiviral Response And Liver Injury In Steatohepatitis In Mice, Timea Csak, Angela Dolganiuc, Karen Kodys, Bharath Nath, Jan Petrasek, Shashi Bala, Dora Lippai, Gyongyi Szabo

Gyongyi Szabo

Mitochondrial dysfunction is a pathogenic feature of nonalcoholic steatohepatitis (NASH). NASH complicates hepatotropic viral disease. The mitochondrial antiviral signaling protein (MAVS) is the adapter of helicase receptors involved in sensing double-stranded RNA (dsRNA). We hypothesized that impaired MAVS function may contribute to insufficient antiviral response and liver damage in steatohepatitis. We identified reduced MAVS protein levels and increased MAVS association with the proteasome subunit alpha type 7 (PSMA7) in livers from mice given a methionine-choline-deficient (MCD) diet. Decreased association of MAVS with mitochondria and increased cytosolic cytochrome c indicated mitochondrial damage in steatohepatitis. In vivo administration of the synthetic dsRNA …

An Essential Role For Monocyte Chemoattractant Protein-1 In Alcoholic Liver Injury: Regulation Of Proinflammatory Cytokines And Hepatic Steatosis In Mice, Pranoti Mandrekar, Aditya Ambade, Arlene Lim, Gyongyi Szabo, Donna Catalano

Gyongyi Szabo

The importance of chemokines in alcoholic liver injury has been implicated. The role of the chemokine, monocyte chemoattractant protein-1 (MCP-1), elevated in patients with alcoholic liver disease is not yet understood. Here, we evaluated the pathophysiological significance of MCP-1 and its receptor, chemokine (C-C motif) receptor 2 (CCR2), in alcoholic liver injury. The Leiber-DeCarli diet containing alcohol or isocaloric control diets were fed to wild-type (WT) and MCP-1-deficient knockout (KO) mice for 6 weeks. In vivo and in vitro assays were performed to study the role of MCP-1 in alcoholic liver injury. MCP-1 was increased in Kupffer cells (KCs) as …

Immune Responses In Cystic Fibrosis: Are They Intrinsically Defective?, Dmitry Ratner, Christian Mueller

Christian Mueller

Cystic fibrosis (CF), the most common lethal single-gene disorder affecting Northern Europeans and North Americans, is caused by mutations in the cystic fibrosis transmembrane conductance regulator (CFTR) gene. Cftr is a chloride channel and a regulator of other ion channels, and many aspects of the CF phenotype are directly related to ion channel abnormalities attributable to CFTR mutation. Lung disease is the most common limitation to the quantity and quality of life for patients with CF. One aspect that continues to be enigmatic is the observed alterations in innate and adaptive immune responses to certain pathogens. Altered responses to Pseudomonas …

Pattern Recognition Receptors And The Innate Immune Response To Viral Infection, Mikayla R. Thompson, John J. Kaminski Iii, Evelyn A. Kurt-Jones, Katherine A. Fitzgerald

Katherine A. Fitzgerald

The innate immune response to viral pathogens is critical in order to mobilize protective immunity. Cells of the innate immune system detect viral infection largely through germline-encoded pattern recognition receptors (PRRs) present either on the cell surface or within distinct intracellular compartments. These include the Toll-like receptors (TLRs), the retinoic acid-inducble gene I-like receptors (RLRs), the nucleotide oligomerization domain-like receptors (NLRs, also called NACHT, LRR and PYD domain proteins) and cytosolic DNA sensors. While in certain cases viral proteins are the trigger of these receptors, the predominant viral activators are nucleic acids. The presence of viral sensing PRRs in multiple …