Ralph Tripp

Ralph Tripp
University of Georgia | UGA · Department of Infectious Diseases

PhD

About

406
Publications
41,835
Reads
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18,773
Citations
Citations since 2017
111 Research Items
5911 Citations
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Introduction
My research interest is to develop translational disease intervention approaches for respiratory viruses. My laboratory investigates the mechanisms of immunity and disease pathogenesis associated with respiratory virus infection to better understand the conceptual and functional differences between innate and adaptive immune responses that provide the foundation necessary to facilitate vaccine and antiviral therapeutic protocols. We also examine the cellular and viral regulatory pathways connecting small RNAs, such as miRNAs. I was trained in the field of viral immunity by Laureate Professor Peter C. Doherty, and previously led a research team in respiratory virus immunology studies at the CDC/Atlanta.
Additional affiliations
January 2020 - December 2022
University of Liverpool
Position
  • Professor (Associate)
January 2012 - December 2021
Deakin University
Position
  • Professor (Associate)
January 2006 - present

Publications

Publications (406)
Article
A rapid and cost-effective method to detect the infection of SARS-CoV-2 is fundamental to mitigating the current COVID-19 pandemic. Herein, a surface-enhanced Raman spectroscopy (SERS) sensor with a deep learning algorithm has been developed for the rapid detection of SARS-CoV-2 RNA in human nasopharyngeal swab (HNS) specimens. The SERS sensor was...
Article
Full-text available
Layer-by-layer microparticle (LbL-MP) fabrication was used to produce synthetic vaccines presenting a fusion peptide containing RSV G protein CX3C chemokine motif and a CD8 epitope of the RSV matrix protein 2 (GM2) with or without a covalently linked TLR2 agonist (Pam3.GM2). Immunization of BALB/c mice with either GM2 or Pam3.GM2 LbL-MP in the abse...
Conference Paper
Full-text available
COVID-19 has devastated the entire world for the past couple of years. Timely and efficient detection and identification of a virus are crucial in preventing the wider virus spread. By using intelligent sensors based on Surface-Enhanced Raman Scattering (SERS), it is possible to detect and identify virus automatically. In this study, we successfull...
Article
Full-text available
It is important to understand the features affecting virus replication, fitness, and transmissibility as they contribute to the outcome of infection and affect disease intervention approaches. Respiratory syncytial virus (RSV) is a major contributor to respiratory disease, particularly in the infant and elderly populations. Although first described...
Article
Full-text available
Influenza B viruses (IBV) primarily infect humans, causing seasonal epidemics. The absence of an animal reservoir limits pandemic concern, but IBV infections may cause severe respiratory disease, predominantly in young children and the elderly. The IBV disease burden is largely controlled by seasonal influenza vaccination; however, immunity due to...
Article
Rapid and sensitive pathogen detection is important for prevention and control of disease. Here, we report a label-free diagnostic platform that combines surface-enhanced Raman scattering (SERS) and machine learning for the rapid and accurate detection of thirteen respiratory virus species including SARS-CoV-2, common human coronaviruses, influenza...
Article
Human metapneumovirus (hMPV) is a leading cause of morbidity and hospitalization among children worldwide, however, no vaccines or therapeutics are currently available for hMPV disease prevention and treatment. The hMPV fusion (F) protein is the sole target of neutralizing antibodies. To map the immunodominant epitopes on the hMPV F protein, we iso...
Article
Full-text available
Coronavirus disease 2019 is a public health challenge requiring rapid testing for the detection of infections and transmission. Nucleic acid amplification tests targeting SARS coronavirus 2 (CoV2) are used to detect CoV2 in clinical samples. Real-time reverse transcription quantitative PCR is the standard nucleic acid amplification test for CoV2, a...
Article
Full-text available
The influenza virus has a large clinical burden and is associated with significant mortality and morbidity. The development of effective drugs for the treatment or prevention of influenza is important in order to reduce its impact. Adamantanes and neuraminidase inhibitors are two classes of anti-influenza drugs in which resistance has developed; th...
Article
Full-text available
RNA viruses like SARS-CoV-2, influenza virus, and respiratory syncytial virus (RSV) are dependent on host genes for replication. We investigated if probenecid, an FDA-approved and safe urate-lowering drug that inhibits organic anion transporters (OATs) has prophylactic or therapeutic efficacy to inhibit RSV replication in three epithelial cell line...
Preprint
COVID-19 is a public health challenge requiring rapid testing for detecting infections and transmission. Nucleic acid amplification tests (NAAT) targeting SARS-CoV-2 (CoV2) are used to detect CoV2 in clinical samples.Real-time reverse transcription-quantitative PCR (RT-qPCR) is the standard NAAT for CoV2, although Reverse Transcription Loop-mediate...
Preprint
COVID-19 is a public health challenge requiring rapid testing for detecting infections and transmission. Nucleic acid amplification tests (NAAT) targeting SARS-CoV-2 (CoV2) are used to detect CoV2 in clinical samples.Real-time reverse transcription-quantitative PCR (RT-qPCR) is the standard NAAT for CoV2, although Reverse Transcription Loop-mediate...
Article
Full-text available
Viral replication and transmissibility are the principal causes of endemic and pandemic disease threats. There remains a need for broad-spectrum antiviral agents. The most common respiratory viruses are endemic agents such as coronaviruses, respiratory syncytial viruses, and influenza viruses. Although vaccines are available for SARS-CoV-2 and some...
Preprint
Human metapneumovirus (hMPV) is a leading cause of morbidity and hospitalization among children worldwide, however, no vaccines or therapeutics are currently available for hMPV disease prevention and treatment. The hMPV fusion (F) protein is the sole target of neutralizing antibodies. To map the immunodominant epitopes on the hMPV F protein, we iso...
Article
Over the last 20 years, both severe acute respiratory syndrome coronavirus-1 and severe acute respiratory syndrome coronavirus-2 have transmitted from animal hosts to humans causing zoonotic outbreaks of severe disease. Both viruses originate from a group of betacoronaviruses known as subgroup 2b. The emergence of two dangerous human pathogens from...
Article
A rapid, portable, and cost-effective method to detect the infection of SARS-CoV-2 is fundamental toward mitigating the current COVID-19 pandemic. Herein, a human angiotensin-converting enzyme 2 protein (ACE2) functionalized silver nanotriangle (AgNT) array localized surface plasmon resonance (LSPR) sensor is developed for rapid coronavirus detecti...
Preprint
Full-text available
RNA viruses like SARS-CoV-2, influenza virus, and respiratory syncytial virus (RSV) are dependent on host genes for replication. We investigated if probenecid prophylaxis or treatment inhibited RSV replication in three epithelial cell lines used in RSV studies, i.e., Vero E6 cells, HEp-2 cells, and in primary normal human bronchoepithelial (NHBE) c...
Article
Introduction Respiratory syncytial virus (RSV) is a leading cause of serious lower respiratory tract infection (LRTI) in infants and young children. Palivizumab is a RSV-specific prophylactic for use in high-risk infants but treatment requires monthly injections and only modestly reduces hospitalization. Thus, new immunoprophylactic candidates are...
Article
Full-text available
RSV is a leading cause of respiratory tract disease in infants and the elderly. RSV has limited therapeutic interventions and no FDA-approved vaccine. Gaps in our understanding of virus–host interactions and immunity contribute to the lack of biological countermeasures. This review updates the current understanding of RSV immunity and immunopatholo...
Article
Full-text available
SARS-CoV-2, the etiologic agent of COVID-19, uses ACE2 as a cell entry receptor. Soluble ACE2 has been shown to have neutralizing antiviral activity but has a short half-life and no active transport mechanism from the circulation into the alveolar spaces of the lung. To overcome this, we constructed an ACE2-human IgG1 fusion protein with mutations...
Article
Influenza virus causes seasonal epidemics and sporadic pandemics resulting in morbidity, mortality, and economic losses worldwide. Understanding how to regulate influenza virus replication is important for developing vaccine and therapeutic strategies. Identifying microRNAs (miRs) that affect host genes used by influenza virus for replication can s...
Article
Full-text available
Influenza viruses cause respiratory tract infections and substantial health concerns. Infection may result in mild to severe respiratory disease associated with morbidity and some mortality. Several anti-influenza drugs are available, but these agents target viral components and are susceptible to drug resistance. There is a need for new antiviral...
Article
Full-text available
Respiratory syncytial virus (RSV) is the primary cause of serious lower respiratory tract disease in infants, young children, the elderly and immunocompromised individuals. Therapy for RSV infections is limited to high risk infants and there are no safe and efficacious vaccines. Matrix (M) protein is a major RSV structural protein with a key role i...
Article
Full-text available
The Special Issue titled “Advances in Vaccine Development” contains articles, reviews, and a perspective on advances in vaccine delivery and expression, nanovaccines, epitopes, proteins and adjuvants, and new vaccine platforms. The Special Issue covers topics including viruses, bacteria, and parasites, as well as the development of vaccines, adjuva...
Article
Full-text available
The COVID-19 pandemic caused by the SARS-CoV-2 is a serious health threat causing worldwide morbidity and mortality. Real-time reverse transcription PCR (RT-qPCR) is currently the standard for SARS-CoV-2 detection. Although various nucleic acid-based assays have been developed to aid the detection of SARS-CoV-2 from COVID-19 patient samples, the ob...
Article
Full-text available
Effective vaccines are slowing the COVID-19 pandemic, but SARS-CoV-2 will likely remain an issue in the future making it important to have therapeutics to treat patients. There are few options for treating patients with COVID-19. We show probenecid potently blocks SARS-CoV-2 replication in mammalian cells and virus replication in a hamster model. F...
Article
Full-text available
Respiratory syncytial virus (RSV) or measles virus (MeV) infection modifies host responses through small non-coding RNA (sncRNA) expression. We show that RSV or MeV infection of neuronal cells induces sncRNAs including various microRNAs and transfer RNA fragments (tRFs). We show that these tRFs originate from select tRNAs (GCC and CAC for glycine,...
Article
Full-text available
Purpose: SARS-CoV-2 infection is associated with substantial mortality and high morbidity. This study tested the effect of angiotensin II type I receptor blocker, losartan, on SARS-CoV-2 replication and inhibition of the papain-like protease of the virus. Methods: The dose-dependent inhibitory effect of losartan, in concentrations from 1μM to 10...
Article
Significance Influenza infections kill millions of people worldwide. Current prophylactic treatment options are limited due to viral strain–specific vaccinations and emerging drug resistance. It is important to discover new immune mechanisms that can fight the influenza virus. Our work presented here identifies such a mechanism. The Duox1 protein h...
Article
Human metapneumovirus (hMPV) is an important cause of acute viral respiratory infection. As the only target of neutralizing antibodies, the hMPV fusion (F) protein has been a major focus for vaccine development and targeting by drugs and monoclonal antibodies (mAbs). While X-ray structures of trimeric pre-fusion and post-fusion hMPV F proteins from...
Article
Full-text available
The novel coronavirus disease 2019 (COVID-19) caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is responsible for the recent global pandemic. The nuclear export protein (XPO1) has a direct role in the export of SARS-CoV proteins including ORF3b, ORF9b, and nucleocapsid. Inhibition of XPO1 induces anti-inflammatory, anti-vi...
Preprint
Full-text available
Effective vaccines are slowing the COVID-19 pandemic, but SARS-CoV-2 will likely remain an issue in the future making it important to have therapeutics to treat patients. There are few options for treating patients with COVID-19. We show probenecid potently blocks SARS-CoV-2 replication in mammalian cells and virus replication in a hamster model. F...
Preprint
Human metapneumovirus (hMPV) is an important cause of acute viral respiratory infection. As the only target of neutralizing antibodies, the hMPV fusion (F) protein has been a major focus for vaccine development and targeting by drugs and monoclonal antibodies (mAbs). While X-ray structures of trimeric pre-fusion and post-fusion hMPV F proteins from...
Article
Swine influenza virus (SIV) can cause respiratory illness in swine. Swine contribute to influenza virus reassortment as avian, human, and/or SIV viruses can infect swine, reassort, and new viruses can emerge. Thus, it is important to determine the host antiviral responses that affect SIV replication. In this study, we examined the innate antiviral...
Article
Full-text available
Vaccines and therapeutics targeting viral surface glycoproteins are a major component of disease prevention for respiratory viral diseases. Over the years, vaccines have proven to be the most successful intervention for preventing disease. Technological advances in vaccine platforms that focus on viral surface glycoproteins have provided solutions...
Article
Full-text available
Respiratory syncytial virus (RSV) infection can cause bronchiolitis, pneumonia, morbidity, and some mortality, primarily in infants and the elderly, for which no vaccine is available. The RSV attachment (G) protein contains a central conserved domain (CCD) with a CX3C motif implicated in the induction of protective antibodies, thus vaccine candidat...
Article
Full-text available
Influenza A virus (IAV) and SARS-CoV-2 (COVID-19) cause pandemic infections where cytokine storm syndrome and lung inflammation lead to high mortality. Given the high social and economic cost of respiratory viruses, there is an urgent need to understand how the airways defend against virus infection. Here we use mice lacking the WD and linker domai...
Article
Influenza virus causes epidemics and sporadic pandemics resulting in morbidity, mortality and economic losses. Influenza viruses require host genes to replicate. RNA interference (RNAi) screens can identify host genes coopted by influenza for replication. Targeting these pro-influenza genes can provide therapeutic strategies to reduce virus replica...
Article
Detection of swine influenza virus (SIV) in commercial swine herds is important for understanding the infection status of the herd and for controlling disease. Current molecular diagnostics require that specimens be submitted to a laboratory which provides results to the growers after some time which is generally too late to intercede in disease co...
Preprint
Full-text available
We present a small molecule chemotype, identified by an orthogonal drug screen, exhibiting nanomolar activity against members of all the six viral families causing most human respiratory viral disease, with a demonstrated barrier to resistance development. Antiviral activity is shown in mammalian cells, including human primary bronchial epithelial...
Preprint
Full-text available
Introduction Coronavirus disease 2019 (COVID-19) can be associated with mortality and high morbidity worldwide. There is an extensive effort to control infection and disease caused by SARS-CoV-2. This study addressed the hypothesis that angiotensin II type I receptor blocker, Losartan, may restrict pathogenesis caused by SARS-CoV-2 by decreasing vi...
Article
Tracking the genetic diversity and spread of swine influenza viruses (SIVs) in commercial swine farms is central for control and to reduce the potential emergence of SIV reassortants. We analyzed the diversity of SIVs in nasal washes or oral fluids from commercial swine farms in North Carolina using influenza M qRT-PCR and hemagglutinin (HA) and ne...
Article
Introduction The innate immune response is the first line of defense against pathogens and consists of physical, chemical and cellular defenses. The adaptive immune response is the second line of defense and is specific to the pathogen. Innate immunity occurs immediately while adaptive immunity develops upon pathogen exposure, and is long-lasting,...
Article
Full-text available
Human norovirus (HuNoV) is a leading cause of acute gastroenteritis. Outbreaks normally occur via the fecal-oral route. HuNoV infection is thought to occur by viral particle transmission, but increasing evidence suggests a function for exosomes in HuNoV infection. HuNoV is contained within stool-derived exosomes, and exosome-associated HuNoV has be...
Article
Full-text available
Respiratory Syncytial Virus (RSV) is the leading cause of lower respiratory tract illness in infants and affects the elderly and the immune-compromised [...]
Preprint
Full-text available
SARS-CoV-2, the etiologic agent of COVID-19, uses ACE2 as a cell entry receptor. Soluble ACE2 has been shown to have neutralizing antiviral activity but has a short half-life and no active transport mechanism from the circulation into the alveolar spaces of the lung. To overcome this, we constructed an ACE2-human IgG1 fusion protein with mutations...
Article
Full-text available
Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the causative agent for COVID-19, is a novel human betacoronavirus that is rapidly spreading worldwide. The outbreak currently includes over 3.7 million cases and 260,000 fatalities. As a betacoronavirus, SARS-CoV-2 encodes for a papain-like protease (PLpro) that is likely responsible fo...
Article
Mumps virus (MuV) caused the most viral meningitis before mass immunization. Unfortunately, MuV has re-emerged in the United States in the past several years. MuV is a member of the family Paramyxoviridae , in the genus Rubulavirus , and has a non-segmented, negative-stranded RNA genome. The viral RNA-dependent RNA polymerase (vRdRps) of MuV consis...
Article
Full-text available
Human norovirus (HuNoV) is a principal cause of acute gastroenteritis worldwide, particularly in developing countries. Its global prevalence is underscored by more serious morbidity and some mortality in the young (<5 years) and the elderly. To date, there are no licensed vaccines or approved therapeutics for HuNoV, mostly because there are limited...
Article
Full-text available
Introduction: Respiratory syncytial virus (RSV) is a leading cause of severe lower respiratory tract disease in young children and a substantial contributor to respiratory tract disease throughout life. Despite RSV being a high priority for vaccine development, there is currently no safe and effective vaccine available. There are many challenges to...
Article
Introduction. Respiratory syncytial virus (RSV) causes lower respiratory tract infections and can lead to morbidity and mortality in the infant, elderly and immunocompromised. There is no vaccine and therapeutic interventions are limited. RSV disease research has yielded the development of several prophylactic and therapeutic treatments. Several pr...
Preprint
Full-text available
Phagocytosis and autophagy represent two evolutionarily ancient pathways that provide an important defense against infection by delivering pathogens to lysosomes for degradation. Phagocytosis and autophagy are linked by non-canonical autophagy pathways that conjugate LC3 to endo-lysosome compartments to facilitate phagosome maturation and lysosome...
Article
Full-text available
[This corrects the article DOI: 10.1371/journal.pbio.1002580.].
Article
Full-text available
Respiratory Syncytial Virus (RSV) causes serious respiratory tract illness and substantial morbidity and some mortality in populations at the extremes of age, i.e., infants, young children, and the elderly. To date, RSV vaccine development has been unsuccessful, a feature linked to the lack of biomarkers available to assess the safety and efficacy...
Article
Full-text available
Background: Rotavirus (RV) is a leading cause of severe gastroenteritis globally and can cause substantial morbidity associated with gastroenteritis in children <5 years of age. Orally administered live-attenuated RV vaccines offer protection against disease but vaccination efforts have been hampered by high manufacturing costs and the need to mai...
Article
Full-text available
The original antigenic sin (OAS) theory considers the outcome of the first encounter with an antigen. It favors a memory response to the original antigen upon exposure to a similar or related antigen, and includes both positive and negative impacts of past exposure on the memory response to challenge, and, in particular, on vaccine efficacy. This p...
Article
Recent progress in understanding the human immune response to respiratory syncytial virus has paved the way for new vaccine antigens and therapeutics to prevent and treat disease. Progress toward understanding the immune response to human metapneumovirus (hMPV) has lagged behind, although hMPV is a leading cause of lower respiratory tract infection...
Article
Full-text available
Viral proteins encode numerous antiviral activities to modify the host immunity. In this article, we hypothesize that viral genomes and gene transcripts interfere with host gene expression using passive mechanisms to deregulate host microRNA (miRNA) activity. We postulate that various RNA viruses mimic or block binding between a host miRNA and its...
Data
Lists analysis of other RNA viruses that also show vSMs and vSSs.
Article
Vaccination remains the most effective means by which influenza virus infection can be controlled. Traditionally vaccine production has focused on egg-based technology. Increasingly cell culture-based vaccine production is being used to improve preparedness. Cell cultured based production methods offer significant advantages over traditional egg-ba...
Article
Human metapneumovirus (hMPV) is a leading cause of lower respiratory tract infection in infants and children, yet there is currently no vaccine available for prevention of hMPV disease. hMPV has three surface proteins: the small hydrophobic, the attachment, and the fusion (F) protein. The hMPV F protein is the sole target of neutralizing antibodies...
Article
Influenza virus infections cause severe morbidity and mortality, especially in high-risk patient populations. Bronchoepithelial cells orchestrate an oxidative antimicrobial system present in the airway liquid consisting of lactoperoxidase, the thiocyanate ion, and hydrogen peroxide. Dual Oxidase 1 (Duox1), an enzyme highly expressed in these cells,...
Article
Full-text available
Respiratory syncytial virus (RSV) is the most common cause of lower respiratory tract disease in children <2 years of age. Increased morbidity and mortality have been reported in high-risk patients, such as premature infants, patients with cardiac disease, and severely immune compromised patients. Severe disease is associated with the virulence of...
Article
Full-text available
Human noroviruses (HuNoVs) are a leading cause of acute gastroenteritis worldwide. HuNoV infections lead to substantial societal and economic burdens. There are currently no licensed vaccines or therapeutics for the prevention or treatment of HuNoVs. A lack of well-characterized in vitro and in vivo infection models has limited the development of H...
Article
Full-text available
To address the unmet needs for human polyclonal antibodies both as therapeutics and diagnostic reagents, building upon our previously established transchromosomic (Tc) cattle platform, we report herein the development of a Tc goat system expressing human polyclonal antibodies in their sera. In the Tc goat system, a human artificial chromosome (HAC)...
Article
Full-text available
Respiratory syncytial virus (RSV) is a leading cause of hospitalization of infants and young children, causing considerable respiratory disease and repeat infections that may lead to chronic respiratory conditions such as asthma, wheezing, and bronchitis. RSV causes ∼34 million new episodes of lower respiratory tract illness (LRTI) in children youn...
Article
Full-text available
Lactoperoxidase (LPO) is an enzyme found in several exocrine secretions including the airway surface liquid producing antimicrobial substances from mainly halide and pseudohalide substrates. Although the innate immune function of LPO has been documented against several microbes, a detailed characterization of its mechanism of action against influen...
Article
Full-text available
The airway epithelium secretes proteins that function in innate defense against infection. BPI fold-containing family member A1 (BPIFA1) is secreted into airways and has a protective role during bacterial infections, but it is not known whether it also has an antiviral role. To determine a role in host defense against influenza A virus (IAV) infect...
Article
Extracellular matrix (ECM) enzymes including the ADAMTS (A disintegrin-like and metalloproteinase with thrombospondin-1 motifs) family have been shown to regulate influenza-specific immunity. ADAMTS7, a largely uncharacterised ECM enzyme with broad tissue distribution has been associated with coronary heart disease and arthritis, however its role i...