A5089857778- HIV Research and Treatment
- Viral Infections and Vectors
- HIV/AIDS drug development and treatment
- Mosquito-borne diseases and control
- Virology and Viral Diseases
- Plant Virus Research Studies
- Virus-based gene therapy research
- RNA and protein synthesis mechanisms
- Bacteriophages and microbial interactions
- Animal Virus Infections Studies
- Viral Infections and Immunology Research
- Fire effects on ecosystems
- CRISPR and Genetic Engineering
- HIV/AIDS Research and Interventions
- Herpesvirus Infections and Treatments
- Immune Cell Function and Interaction
- Cytomegalovirus and herpesvirus research
- Viral gastroenteritis research and epidemiology
- Viral Infections and Outbreaks Research
- Vector-Borne Animal Diseases
- RNA Research and Splicing
- RNA Interference and Gene Delivery
- Bacterial Genetics and Biotechnology
- COVID-19 epidemiological studies
- Animal Disease Management and Epidemiology
Tulane University
2013-2024
University of New Mexico
2001-2010
University of Wisconsin–Madison
1989-2002
Baylor College of Medicine
1998
Fred Hutch Cancer Center
1992
Stanford University
1992
University of Washington
1981-1983
Autophagy is a cytoplasmic degradative pathway that can participate in biosynthetic processes, as the yeast Cvt pathway, but more commonly known for its functions removing damaged or surplus organelles and macromolecular complexes. Here, we find autophagy intersects with human immunodeficiency virus (HIV) biogenesis, mirroring above dichotomy. Early, nondegradative stages of promoted HIV yields. Gag-derived proteins colocalized interacted factor LC3, productive Gag processing. Nevertheless,...
Several domains of the human immunodeficiency virus type 1 (HIV-1) envelope glycoprotein have been identified that are involved in HIV-1-mediated membrane fusion. One domain is fusion hydrophobic amino terminus HIV-1 transmembrane gp41. Here we show a polar substitution at gp41 acid 2 (the 41.2 mutation) results an dominantly interferes with both syncytium formation and infection mediated by wild-type glycoprotein. The interference mutant not result aberrant synthesis, processing, or...
We analyzed the leader region of human immunodeficiency virus type 1 (HIV-1) RNA to decipher nature cis-acting E/psi element required for encapsidation viral into particles. Our data indicate that, encapsidation, there are at least two functional subregions in region. One subregion is located a position immediately proximal major splice donor, and second between donor beginning gag gene. This suggests that discrete elements recognition signals encapsidation. To determine whether specific...
Retroviruses contain two copies of the plus stranded viral RNA genome. As a means determining whether both these RNA's are used in reverse transcription reaction, cells were infected with heterozygous virus particles that varied nucleotide sequence at separate locations termini. The DNA proviruses formed from single cycle then examined. Of 12 characterized, all exhibited long terminal repeats (LTR's) would be expected to arise only if templates for generation minus strand DNA. In contrast,...
We mutagenized cloned spleen necrosis virus DNA to identify a region of the retrovirus genome encoding polypeptide required for integration viral DNA. Five plasmids bearing different lesions in 3' end pol gene were examined ability integrate or replicate following transfection chicken embryo fibroblasts. Transfection with one these DNAs resulted generation mutant incapable integrating but able at low levels; this phenotype is identical that mutants alterations cis-acting region, att. To...
To determine whether there is a cis-acting effect of translational expression gag on RNA encapsidation, we compared the encapsidation wild-type with that mutant in which translation was ablated. This comparison indicated not such cis effect. what necessary and sufficient for measured relative efficiencies human immunodeficiency virus type 1 vector RNAs containing mutations domains proximal to canonical signal or large deletions remainder genome. These data indicate TAR two additional regions...
Packaging of retroviral RNA is attained through the specific recognition a cis-acting encapsidation site (located near 5' end viral RNA) by components Gag precursor protein. Human immunodeficiency virus type 1 (HIV-1) and simian (SIV) are two lentiviruses that lack apparent sequence similarity in their putative regions. We used SIV vectors to determine whether HIV-1 particles can recognize functionally propagate nucleic acid. acid was replicated proteins. Thus, efficient lentivirus...
The minus strand and ambisense segmented RNA viruses include multiple important human pathogens are divided into three families, the Orthomyxoviridae , Bunyaviridae Arenaviridae . These all initiate viral transcription through process of “cap-snatching,” which involves acquisition capped 5′ oligonucleotides from cellular mRNA. Hantaviruses emerging pathogenic family that replicate in cytoplasm infected cells. Cellular mRNAs can be actively translated polysomes or physically sequestered...
Tat-dependent expression of an endogenous lethal or deleterious foreign gene might be useful for abrogating the production human immunodeficiency virus (HIV) from cells. This type HIV-induced cellular killing, as well other approaches to therapy HIV infection, would facilitated by simple vectors that express introduced genes in a Tat-inducible manner. As part studies examine feasibility this concept, we constructed HIV-1 hygromycin B phosphotransferase (Hygr) Comparison efficiency...
Abstract Zika virus (ZIKV) infection of pregnant women is associated with pathologic complications fetal development. Here, we infect rhesus macaques ( Macaca mulatta ) a minimally passaged ZIKV isolate from Rio de Janeiro, where high rate development was observed. The this results in maternal viremia, crossing into the amniotic fluid (AF), and utero deaths. We also treated three additional ZIKV-infected cocktail ZIKV-neutralizing human monoclonal antibodies (nmAbs) at peak viremia. While...
At least two hairpins in the 5' untranslated leader region, stem-loops 1 and 3 (SL1 SL3), contribute to human immunodeficiency virus type RNA encapsidation vivo. We used a competitive assay, which measures relative efficiency of mutant viral presence competing wild-type RNA, compare contributions SL1, SL3, adjacent secondary structures, SL2 SL4, encapsidation. is not required for encapsidation, while SL4 all approximately equally To determine whether these function position-dependent manner,...
Cells expressing specific proviruses are resistant to superinfection by viruses of the same subgroup. To investigate role reticuloendotheliosis virus (REV) envelope glycoprotein (env-gp) in establishment resistance superinfection, we constructed plasmids that express either wild-type env-gp or an derivative lacks part transmembrane (TM) protein. After transfection, transient expression env gene resulted syncytium formation a mammalian cell line permissive for replication, whereas synthesis...
Hantaviruses are tripartite negative-sense RNA viruses and members of the Bunyaviridae family. The nucleocapsid (N) protein is encoded by smallest three genome segments (S). N principal structural component viral capsid central to hantavirus replication cycle. We examined intermolecular N-protein interaction binding using bacterially expressed Sin Nombre virus protein. assembles into di- trimeric forms. mono- dimeric forms exist transiently assemble a form. In contrast, trimer highly stable...
Hantaviruses are tripartite negative-sense RNA viruses and members of the Bunyaviridae family. The nucleocapsid (N) protein is principal structural component viral capsid. N forms a stable trimer that specifically recognizes panhandle structure formed by termini. We used trimeric glutathione S-transferase (GST)-N small panhandles to examine requirements for specific recognition Sin Nombre hantavirus N. Trimeric GST-N three RNAs (S, M, L) with high affinity, whereas corresponding plus-strand...
Cellular RNA chaperones are crucial for the genesis of correctly folded functional RNAs. Using several complementary in vitro assays we find that bunyavirus nucleocapsid protein (N) is an chaperone. In Bunyaviridae genomic stable “panhandle” formation arises through hydrogen bonding terminal nucleotides RNA. The chaperone function N facilitates panhandle even though termini separated by >2 kb. likely driven exceptionally high base-pairing specificity as evidenced P-num analysis. can...
The reticuloendotheliosis viruses (REV) are a family of highly related retroviruses isolated from gallinaceous birds. On the basis sequence comparison and overall genome organization, these more similar to mammalian type C than avian sarcoma/leukemia viruses. envelope member REV family, spleen necrosis virus (SNV), is about 50% identical in amino acid D simian retroviruses. Although SNV does not productively infect primate or murine cells, receptor for present on variety human cells....
Hantaviruses are tripartite negative-sense RNA viruses and members of the Bunyaviridae family. The nucleocapsid (N) protein, encoded by smallest three genome segments (S), has nonspecific chaperone activity. This activity results in transient dissociation misfolded structures, may be required for facilitating correct higher-order structure, function viral replication. We carried out a series experiments to further characterize ability N dissociate duplexes. As might expected, dissociated...
Abstract Zika virus (ZIKV) is a flavivirus that can cause neuropathogenesis in adults and fetal neurologic malformation following the infection of pregnant women. We used nonhuman primate model, Indian‐origin Rhesus macaque (IRM), to gain insight into virus‐associated hallmarks ZIKV‐induced adult neuropathology. find causes prevalent acute chronic neuroinflammation disruption blood‐brain barrier (BBB) animals. ZIKV resulted specific short‐ long‐term augmented expression chemokine CXCL12...