A5037696772- Cytomegalovirus and herpesvirus research
- HIV Research and Treatment
- Viral-associated cancers and disorders
- Herpesvirus Infections and Treatments
- HIV/AIDS drug development and treatment
- interferon and immune responses
- RNA regulation and disease
- Toxoplasma gondii Research Studies
- RNA modifications and cancer
- CRISPR and Genetic Engineering
- Virology and Viral Diseases
- Biochemical and Molecular Research
- Polyomavirus and related diseases
- Advanced Electron Microscopy Techniques and Applications
- Lymphoma Diagnosis and Treatment
- Mosquito-borne diseases and control
University of Minnesota
2018-2023
Masonic Cancer Center
2018-2022
University of Minnesota Medical Center
2018-2021
The University of Texas Southwestern Medical Center
2016
Bats have attracted attention in recent years as important reservoirs of viruses deadly to humans and other mammals. These infections are typically nonpathogenic bats raising questions about innate immune differences that might exist between The APOBEC3 gene family encodes antiviral DNA cytosine deaminases with roles the suppression diverse genomic parasites. Here, we characterize pteropid genes show species within genus Pteropus possess largest most array identified any mammal reported...
The APOBEC3 family of DNA cytosine deaminases constitutes a vital innate immune defense against range different viruses. A novel counterrestriction mechanism has recently been uncovered for the gammaherpesvirus EBV, in which subunit viral protein known to produce building blocks (ribonucleotide reductase) causes A3B relocalize from nucleus cytosol. Here, we extend these observations with include closely related gammaherpesvirus, KSHV, and more distantly alphaherpesvirus, HSV-1. These...
Viruses use a plethora of mechanisms to evade immune responses. A recent example is neutralization the nuclear DNA cytosine deaminase APOBEC3B by Epstein-Barr virus (EBV) ribonucleotide reductase subunit BORF2. Cryo-EM studies APOBEC3B-BORF2 complexes reveal large >1000-Å 2 binding surface composed multiple structural elements from each protein, which effectively blocks active site accessing single-stranded substrates. Evolutionary optimization suggested unique insertions in BORF2 absent...
ABSTRACT HIV-1 must overcome multiple innate antiviral mechanisms to replicate in CD4 + T lymphocytes and macrophages. Previous studies have demonstrated that the apolipoprotein B mRNA editing enzyme polypeptide-like 3 (APOBEC3, A3) family of proteins (at least A3D, A3F, A3G, stable A3H haplotypes) contribute restriction lymphocytes. Virus-encoded virion infectivity factor (Vif) counteracts this activity by degrading A3 enzymes allowing replication infected cells. In addition proteins, Vif...
Human APOBEC3H (A3H) is a single-stranded DNA cytosine deaminase that inhibits HIV-1. Seven haplotypes (I-VII) and four splice variants (SV154/182/183/200) with differing antiviral activities geographic distributions have been described, but the genetic mechanistic basis for variant expression function remains unclear. Using combined bioinformatic/experimental analysis, we find SV200 specific to haplotype II, which primarily found in sub-Saharan Africa. The underlying mechanism differential...
The APOBEC3 family of DNA cytosine deaminases comprises an important arm the innate antiviral defense system. gamma-herpesviruses Epstein-Barr virus and Kaposi's sarcoma-associated herpesvirus alpha-herpesviruses herpes simplex (HSV)-1 HSV-2 have evolved efficient mechanism to avoid restriction by directly binding APOBEC3B facilitating its exclusion from nuclear compartment. only viral protein required for relocalization is large subunit ribonucleotide reductase (RNR). Here, we ask whether...
Viruses have evolved diverse mechanisms to antagonize host immunity such as direct inhibition and relocalization of cellular APOBEC3B (A3B) by the ribonucleotide reductase (RNR) Epstein-Barr virus. Here, we investigate mechanistic conservation evolutionary origin this innate immune counteraction strategy. First, find that human gamma-herpesvirus RNRs engage A3B via largely distinct surfaces. Second, show RNR-mediated enzymatic depend upon binding different regions catalytic domain. Third,...
Significance We show that the autophagy-related protein Beclin 2 functions as a newly described cellular regulator of viral G protein-coupled receptors (GPCRs) and suppressor GPCR-driven tumorigenesis. in regulating Kaposi’s sarcoma-associated herpesvirus-encoded GPCR levels, proinflammatory signaling, oncogenic activity mice by facilitating endolysosomal trafficking. This 2-dependent trafficking degradation an may represent broader heretofore unappreciated role machinery innate immunity (by...
APOBEC enzymes are DNA cytosine deaminases that normally serve as virus restriction factors, but several members, including APOBEC3H, also contribute to cancer mutagenesis. Despite their importance in multiple fields, little is known about cellular processes regulate these mutating enzymes. We show APOBEC3H exists two distinct subcellular compartments, cytoplasm and nucleolus, the structural determinants for each mechanism genetically separable. First, native fluorescently tagged APOBEC3Hs...
Herpesvirus lytic infection causes cells to arrest at the G1/S phase of cell cycle by poorly defined mechanisms. In a prior study using fluorescent ubiquitination-based indicator (FUCCI) that express fluorescently tagged proteins marking different stages cycle, we showed Epstein-Barr virus (EBV) protein BORF2 induces accumulation cells, and affects p53 levels without affecting target p21. We also found specifically interacted with APOBEC3B (A3B) forms perinuclear bodies A3B prevent from...
The APOBEC3 family of DNA cytosine deaminases comprises an important arm the innate antiviral defense system. gamma-herpesviruses EBV and KSHV alpha-herpesviruses HSV-1 HSV-2 have evolved efficient mechanism to avoid restriction by directly binding APOBEC3B facilitating its exclusion from nuclear compartment. only viral protein required for relocalization is large subunit ribonucleotide reductase (RNR). Here, we ask whether this conserved with beta-herpesvirus human cytomegalovirus (HCMV)....
HIV-1 must overcome multiple innate antiviral mechanisms to replicate in CD4 + T lymphocytes and macrophages. Previous studies have demonstrated that the APOBEC3 (A3) family of proteins (at least A3D, A3F, A3G, stable A3H haplotypes) contribute restriction lymphocytes. Virus-encoded virion infectivity factor (Vif) counteracts this activity by degrading A3 enzymes allowing replication infected cells. In addition proteins, Vif also targets other cellular lymphocytes, including PPP2R5 proteins....
Abstract An integral part of the antiviral innate immune response is APOBEC3 family single-stranded DNA cytosine deaminases, which inhibits virus replication through deamination-dependent and -independent activities. Viruses have evolved mechanisms to counteract these enzymes such as HIV-1 Vif-mediated formation a ubiquitin ligase degrade virus-restrictive enzymes. A new example Epstein-Barr (EBV) ribonucleotide reductase (RNR)-mediated inhibition cellular APOBEC3B (A3B). The large subunit...
Abstract Viruses use a plethora of mechanisms to evade immune responses. A new example is neutralization the nuclear DNA cytosine deaminase APOBEC3B by Epstein-Barr virus (EBV) ribonucleotide reductase subunit BORF2. Cryo-EM studies APOBEC3B-BORF2 complexes reveal large >1000 Å 2 binding surface comprised multiple structural elements from each protein, which effectively blocks active site accessing single-stranded substrates. Evolutionary optimization suggested unique insertions in BORF2...
Abstract Viruses have evolved diverse mechanisms to antagonize host immunity such as direct inhibition and relocalization of cellular APOBEC3B (A3B) by the ribonucleotide reductase (RNR) Epstein-Barr virus. Here, we investigate mechanistic conservation evolutionary origin this innate immune counteraction strategy. First, find that human gamma-herpesvirus RNRs engage A3B via largely distinct surfaces. Second, show RNR-mediated enzymatic depend upon binding different regions catalytic domain....