A5064725929- HIV Research and Treatment
- Immune Cell Function and Interaction
- interferon and immune responses
- Viral Infections and Vectors
- Viral Infections and Outbreaks Research
- Herpesvirus Infections and Treatments
- Viral gastroenteritis research and epidemiology
- HIV/AIDS drug development and treatment
- Signaling Pathways in Disease
- Cytomegalovirus and herpesvirus research
- T-cell and B-cell Immunology
- Neurogenesis and neuroplasticity mechanisms
- Adipose Tissue and Metabolism
- Viral Infections and Immunology Research
- Nerve injury and regeneration
- Memory and Neural Mechanisms
- Autism Spectrum Disorder Research
- Neuropeptides and Animal Physiology
- Parvovirus B19 Infection Studies
- Animal Virus Infections Studies
- Respiratory viral infections research
- Cardiovascular Disease and Adiposity
- Regulation of Appetite and Obesity
- SARS-CoV-2 and COVID-19 Research
- Immune Response and Inflammation
National Institute on Aging
2018-2025
Johns Hopkins Medicine
2024
Johns Hopkins University
2024
National Institutes of Health
2018
Harvard University
2004-2015
Broad Institute
2012-2015
Center for Systems Biology
2012-2015
Massachusetts Institute of Technology
2012
Dana-Farber Cancer Institute
2004-2010
American Association For The Advancement of Science
2007
The host restriction factor TRIM5α mediates species-specific, early blocks to retrovirus infection; susceptibility these is determined by viral capsid sequences. Here we demonstrate that variants from Old World monkeys specifically associate with the HIV type 1 (HIV-1) and this interaction depends on B30.2 domain. Human New monkey proteins associated less efficiently HIV-1 capsid, accounting for lack of in cells species. After infection, expression a restricting target correlated decrease...
Retroviruses encounter dominant postentry restrictions in cells of particular species. Human immunodeficiency virus type 1 (HIV-1) is blocked the Old World monkeys by TRIM5alpha, a tripartite motif (TRIM) protein composed RING, B-box 2, coiled-coil, and B30.2(SPRY) domains. Rhesus monkey TRIM5alpha (TRIM5alpha(rh)) more potently blocks HIV-1 infection than human (TRIM5alpha(hu)). Here, studying chimeric proteins, we demonstrate that major determinant anti-HIV-1 potency domain. Analysis...
Murine leukemia viruses (MLVs) have been classified as N-tropic (N-MLV) or B-tropic (B-MLV), depending on their ability to infect particular mouse strains. The early phase of N-MLV infection is blocked in the cells several mammalian species, including humans. This block mediated by a dominant host factor that targets viral capsid soon after virus entry into cell has achieved. A similar HIV-1 rhesus monkey TRIM5α. Here we show human TRIM5α both necessary and sufficient for restriction cells....
The TRIM5alpha proteins of humans and some Old World monkeys have been shown to block infection particular retroviruses following virus entry into the host cell. Infection most New monkey cells by simian immunodeficiency macaques (SIVmac) is restricted at a similar point. Here we examine antiretroviral activity orthologs from humans, apes, monkeys, monkeys. Chimpanzee orangutan functionally resembled human TRIM5alpha, potently restricting N-tropic murine leukemia (N-MLV) moderately type 1...
ABSTRACT Tripartite motif (TRIM) proteins are composed of RING, B-box 2, and coiled coil domains. Some TRIM proteins, such as TRIM5α, also possess a carboxy-terminal B30.2(SPRY) domain localize to cytoplasmic bodies. TRIM5α has recently been shown mediate innate intracellular resistance retroviruses, an activity dependent on the integrity B30.2 domain, in particular primate species. An examination sequences several related TRIM5 revealed existence four variable regions (v1, v2, v3, v4)...
We have developed a robust RNA sequencing method for generating complete de novo assemblies with intra-host variant calls of Lassa and Ebola virus genomes in clinical biological samples. Our uses targeted RNase H-based digestion to remove contaminating poly(rA) carrier ribosomal RNA. This depletion step improves both the quality data quantity informative reads unbiased total libraries. also hybrid-selection protocol further enrich viral content These protocols enabled rapid deep are broadly...
We have developed a robust RNA sequencing method for generating complete de novo assemblies with intra-host variant calls of Lassa and Ebola virus genomes in clinical biological samples. Our uses targeted RNase H-based digestion to remove contaminating poly(rA) carrier ribosomal RNA. This depletion step improves both the quality data quantity informative reads unbiased total libraries. also hybrid-selection protocol further enrich viral content These protocols enabled rapid deep are broadly...
Increasing evidence indicates that physical activity and exercise training may delay or prevent the onset of Alzheimer’s disease (AD). However, systemic biomarkers can measure effects on brain function link to relevant metabolic responses are lacking. To begin address this issue, we utilized blood samples 23 asymptomatic late middle-aged adults, with familial genetic risk for AD (mean age 65 years old, 50% female) who underwent 26 weeks supervised treadmill training. Systemic implicated in...
TRIM5alpha is a cytoplasmic protein that mediates post-entry block to infection by some retroviruses. contains tripartite motif (TRIM), which includes RING, B-box 2, and coiled-coil domains, C-terminal B30.2 (SPRY) domain. We investigated the contribution of RING 2 domains antiretroviral activity rhesus monkey (TRIM5alpharh), potently restricts human immunodeficiency virus, type 1 (HIV-1) simian virus African green monkeys (SIVagm). Disruption domain caused mislocalization TRIM5alpharh so...
Human TRIM5alpha (TRIM5alpha(hu)) only modestly inhibits human immunodeficiency virus type 1 (HIV-1) and does not inhibit simian (SIV(mac)). Alteration of arginine 332 in the TRIM5alpha(hu) B30.2 domain to proline, residue found rhesus monkey TRIM5alpha, has been shown create a potent restricting factor for both HIV-1 SIV(mac.) Here we demonstrate that potentiation inhibition results from removal positively charged at position TRIM5alpha(hu.) The increase activity correlated with an ability...
The host cell factors TRIM5alpha(hu) and Fv-1 restrict N-tropic murine leukemia virus (N-MLV) infection at an early postentry step before or after reverse transcription, respectively. Interestingly, the identity of residue 110 MLV capsid determines susceptibility to both Fv-1. In this study, we investigate fate in cells expressing either restriction factor. expression TRIM5alpha(hu), but not Fv-1, specifically promoted premature conversion particulate N-MLV capsids within infected soluble...
The retrovirus restriction factor TRIM5alpha targets the viral capsid soon after entry. Here we show that protein oligomerizes into trimers. coiled-coil and B30.2(SPRY) domains make important contributions to formation and/or stability of A functionally defective mutant with RING B-box 2 deleted can form heterotrimers wild-type TRIM5alpha, accounting for observed dominant-negative activity protein. Trimerization potentially allows interact threefold pseudosymmetrical structures on retroviral capsids.
Next-generation sequencing (NGS) has the potential to transform discovery of viruses causing unexplained acute febrile illness (UAFI) because it does not depend on culturing pathogen or a priori knowledge pathogen's nucleic acid sequence. More generally, elucidate complete human virome, including that cause no overt symptoms disease, but may have unrecognized immunological developmental consequences. We used NGS identify RNA in blood 195 patients with UAFI and compared them those found 328...
In cells of Old World and some New monkeys, dominant factors restrict human immunodeficiency virus type 1 (HIV-1) infections after entry. The simian SIV(mac) is less susceptible to these restrictions, a property that determined largely by the viral capsid protein. For this study, we altered exposed amino acid residues on surface HIV-1 capsid, changing them corresponding found capsid. We identified two distinct pathways escape from early, postentry restriction in monkey cells. One set mutants...
Rhesus TRIM5alpha (rhTRIM5alpha), but not human (huTRIM5alpha), potently inhibits immunodeficiency virus (HIV) infection and is thus a potentially valuable therapeutic tool. Primary CD4 T cells engineered to express rhTRIM5alpha were highly resistant cell-free HIV type 1 (HIV-1) infection. However, when cocultured with unmodified cells, rhTRIM5alpha-expressing became permissive HIV-1 Physical separation of revealed that efficiently restricts cell-associated transmission. Furthermore, we...