A5022339508- HIV Research and Treatment
- Immune Cell Function and Interaction
- T-cell and B-cell Immunology
- Cytomegalovirus and herpesvirus research
- SARS-CoV-2 and COVID-19 Research
- interferon and immune responses
- Immunotherapy and Immune Responses
- Animal Virus Infections Studies
- Virus-based gene therapy research
- COVID-19 Clinical Research Studies
- Viral gastroenteritis research and epidemiology
- Vector-Borne Animal Diseases
- Long-Term Effects of COVID-19
- Probiotics and Fermented Foods
- Virology and Viral Diseases
- RNA regulation and disease
- Animal Disease Management and Epidemiology
- Herpesvirus Infections and Treatments
- SARS-CoV-2 detection and testing
- Viral Infections and Outbreaks Research
- Influenza Virus Research Studies
- Monoclonal and Polyclonal Antibodies Research
- Chromosomal and Genetic Variations
- Complement system in diseases
- Traditional Chinese Medicine Studies
University of Colorado Anschutz Medical Campus
2016-2024
University of Colorado Denver
2014-2024
Aurora University
2016
China Medical University
2015
University of Denver
2012
Beijing University of Agriculture
2011
Auburn University
2007-2011
The emergence of SARS-CoV-2 variants with enhanced transmissibility, pathogenesis, and resistance to vaccines presents urgent challenges for curbing the COVID-19 pandemic. While Spike mutations that enhance virus infectivity or neutralizing antibody evasion may drive these novel variants, studies documenting a critical role interferon responses in early control infection, combined presence viral genes limit responses, suggest interferons also influence evolution. Here, we compared potency 17...
The impacts of interferon (IFN) signaling on COVID-19 pathology are multiple, with both protective and harmful effects being documented. We report here a multiomics investigation systemic IFN in hospitalized patients, defining the biosignatures associated varying levels 12 different type I, II, III IFNs. antiviral transcriptional response circulating immune cells is strongly specific subset IFNs, most prominently IFNA2 IFNG. In contrast, proteomics signatures indicative endothelial damage...
ABSTRACT Human papillomaviruses (HPVs) are small DNA viruses causally associated with benign warts and multiple cancers, including cervical head-and-neck cancers. While the vast majority of people exposed to HPV, most instances infection cleared naturally. However, intrinsic host defense mechanisms that block early establishment HPV infections remain mysterious. Several antiviral cytidine deaminases human APOBEC3 (hA3) family have been identified as potent viral mutators. editing genomes in...
Objective: Gut microbial translocation is a major driving force behind chronic immune activation during HIV-1 infection. HIV-1-related intestinal dysbiosis, including increases in mucosa-associated pathobionts, may influence and contribute to mucosal systemic inflammation. Thus, it critical understand the mechanisms by which gut microbes their metabolic products, such as butyrate, cell function Design: A cross-sectional study was performed compare relative abundance of butyrate-producing...
Although all 12 subtypes of human interferon alpha (IFN-α) bind the same receptor, recent results have demonstrated that they elicit unique host responses and display distinct efficacies in control different viral infections. The IFN-α2 subtype is currently HIV-1 clinical trials, but it has not consistently reduced loads patients most effective against vitro We now demonstrate humanized mice that, when delivered at high dose, IFN-α14 very potent anti-HIV-1 activity whereas does not. In both...
HIV-1 is transmitted primarily across mucosal surfaces and rapidly spreads within the intestinal mucosa during acute infection. The type I interferons (IFNs) likely serve as a first line of defense, but relative expression antiviral properties 12 IFNα subtypes against infection tissues remain unknown. Here, we evaluated all in HIV-1-exposed plasmacytoid dendritic cells by next-generation sequencing. We then determined potency each subtype ex vivo using human Lamina Propria Aggregate Culture...
Abstract The emergence of SARS-CoV-2 variants with enhanced transmissibility, pathogenesis and resistance to vaccines presents urgent challenges for curbing the COVID-19 pandemic. While Spike mutations that enhance virus infectivity or neutralizing antibody evasion may drive these novel variants, studies documenting a critical role interferon responses in early control infection, combined presence viral genes limit responses, suggest interferons also influence evolution. Here, we compared...
Innate immune signaling is essential for clearing pathogens and damaged cells must be tightly regulated to avoid excessive inflammation or autoimmunity. Here, we found that the alternative splicing of exons derived from transposable elements a key mechanism controlling in human cells. By analyzing long-read transcriptome datasets, identified numerous transposon exonization events predicted generate functional protein variants genes, including type I interferon receptor IFNAR2. We...
Early HIV-1 infection is characterized by high levels of replication and substantial CD4 T cell depletion in the intestinal mucosa, epithelial barrier breakdown, microbial translocation. HIV-1-induced disruption homeostasis has also been associated with changes microbiome that are linked to mucosal systemic immune activation. In this study, we investigated impact representative bacterial species were altered colonic mucosa viremic infected individuals (HIV-altered bacteria; HAMB) on...
ABSTRACT APOBEC3 (A3) mutation signatures have been observed in a variety of human cancer genomes, including those cervical and head neck cancers caused by papillomavirus (HPV) infection. However, the driving forces that promote off-target A3 activity remain mostly unclear. Here, we report mechanism for dramatic increase A3A protein levels HPV-positive keratinocytes. We show expression viral E7 from high-risk HPVs, but not low-risk significantly prolongs cellular half-life keratinocytes cell...
Severe coronavirus disease 2019 (COVID-19) has been associated with T cell lymphopenia, but no causal effect of deficiency on severity established. To investigate the specific role cells in recovery from severe acute respiratory syndrome 2 (SARS-CoV-2) infections, we studied rhesus macaques that were depleted either CD4+, CD8+, or both subsets prior to infection. Peak virus loads similar all groups, resolution cell-depleted animals was slightly delayed compared controls. The groups developed...
Endogenous retroelements (EREs), including human endogenous retroviruses (HERVs) and long interspersed nuclear elements (LINEs), comprise almost half of the genome. Our previous studies interferome in gut suggest potential mechanisms regarding how IFNb may drive HIV-1 pathogenesis. As ERE activity is suggested to partake type 1 immune responses incredibly sensitive viral infections, we sought elucidate underlying interactions between expression dynamics people living with (PLWH).
Tetherin is a membrane protein of unusual topology expressed from rodents to humans that accumulates enveloped virus particles on the surface infected cells. However, whether this 'tethering' activity promotes or restricts retroviral spread during acute retrovirus infection in vivo controversial. We report here identification single nucleotide polymorphism gene NZW/LacJ (NZW) mice mutated canonical ATG start site GTG. Translation NZW downstream ATGs deleted conserved dual-tyrosine endosomal...
Significance Antibodies are important for recovery from viral infections and vaccine efficacy. To improve the ability of antibodies to bind neutralize pathogens, antibody DNA sequences undergo a mutational process driven by enzyme activation-induced deaminase (AID). However, high levels mutations required potently inhibit global strains retrovirus HIV-1. We provide evidence that related enzyme, apolipoprotein B mRNA-editing catalytic polypeptide 3 (APOBEC3), can also mutate during infection,...
Follicular regulatory T (TFR) cells are a subset of CD4+ in secondary lymphoid follicles. TFR were previously included the follicular helper (TFH) cell subset, which consists that highly permissive to HIV-1. The permissivity HIV-1 is unknown. We find more than TFH R5-tropic ex vivo expressed CCR5 and CD4 supported higher frequencies viral fusion. Differences Ki67 expression correlated with replication. Inhibiting cellular proliferation reduced Lymph node from untreated HIV-infected...
Global transcriptome studies can help pinpoint key cellular pathways exploited by viruses to replicate and cause pathogenesis. Previous data showed that laboratory-adapted HIV-1 triggers significant gene expression changes in CD4+ T cell lines mitogen-activated cells from peripheral blood. However, primarily targets mucosal compartments during acute infection vivo. Moreover, early causes extensive depletion of the gastrointestinal tract herald persistent inflammation due translocation...
The Type I Interferons (IFN-Is) are innate antiviral cytokines that include 12 different IFNα subtypes and IFNβ signal through the IFN-I receptor (IFNAR), inducing hundreds of IFN-stimulated genes (ISGs) comprise 'interferome'. Quantitative differences in IFNAR binding correlate with activity, but whether IFN-Is exhibit qualitative remains controversial. Moreover, response is protective during acute HIV-1 infection, likely pathogenic chronic stages. To gain a deeper understanding response,...
Abstract Tetherin/BST-2 is a host restriction factor that inhibits retrovirus release from infected cells in vitro by tethering nascent virions to the plasma membrane. However, contradictory data exists on whether Tetherin acute infection vivo . Previously, we reported Tetherin-mediated inhibition of Friend (FV) replication at 2 weeks post-infection correlated with stronger natural killer, CD4+ T and CD8+ cell responses. Here, further investigated role counteracting FV levels were similar...
Members of the APOBEC3 family deoxycytidine deaminases counteract a broad range retroviruses in vitro through an indirect mechanism that requires virion incorporation and inhibition reverse transcription and/or hypermutation minus strand transcripts next target cell. The selective advantage to host this restriction remains unclear, but valuable insights may be gained by studying function vivo. Apobec3 was previously shown encode Rfv3, classical resistance gene controls recovery mice from...
Infection by human papillomavirus (HPV) is a necessary cause of cervical cancer. The purpose this study was to investigate the prevalence and genotype distribution HPV infection in Chinese women who were asymptomatic for diseases. Cervical cytology samples collected from 6479 Liaoning province, tested various genotypes using chip hybridization assay. found 10.3% all studied, with high risk (HR HPV) low (LR being 9.5% 1.1%, respectively. 16, 52, 58 most frequently HR positive women, present...
Objective(s): Type I interferon (IFN-I) responses confer both protective and pathogenic effects in persistent virus infections. IFN-I diversity, stage of infection tissue compartment may account for this dichotomy. The gut is a major site early HIV-1 replication microbial translocation, but the nature response remains unclear. Design: Samples were obtained from two IRB-approved cross-sectional studies. first study included individuals with chronic, untreated (n = 24) age/sex-balanced...