Publications by authors named "Julia DeVoto"

4 Publications

  • Page 1 of 1

Ct Values Do not Predict SARS-CoV-2 Transmissibility in College Students.

J Mol Diagn 2021 Jun 5. Epub 2021 Jun 5.

Department of Pathology and Laboratory Medicine, Tulane University, New Orleans, Louisiana. Electronic address:

Severe acute respiratory syndrome coronavirus 2 is highly contagious, and the global spread has caused significant medical/socioeconomic impacts. Other than vaccination, effective public health measures (including contact tracing, isolation, and quarantine) are critical for deterring viral transmission, preventing infection progression, and resuming normal activities. Viral transmission is affected by many factors, but the viral load and vitality could be among the most important ones. Although in vitro studies have indicated that the amount of virus isolated from infected people affects the successful rate of virus isolation, whether the viral load carried at the individual level would determine the transmissibility was unknown. We aimed to examine, from a diagnostic point of view, whether the cycle threshold (Ct) value, a measurement of viral load by RT-PCR assay, could differentiate the spreaders from the nonspreaders in a population of college students. Our results indicate that although at the population level the Ct value is lower (suggesting a higher viral load) in the symptomatic spreaders than in the asymptomatic nonspreaders, there is significant overlap in the Ct values between the two groups. Thus, the Ct value, or the viral load, at the individual level could not predict transmissibility. Our studies also suggest that a sensitive method to detect the presence of virus is needed to identify asymptomatic persons who may carry a low viral load but can still be infectious.
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http://dx.doi.org/10.1016/j.jmoldx.2021.05.012DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8178946PMC
June 2021

Heightened resistance to host type 1 interferons characterizes HIV-1 at transmission and after antiretroviral therapy interruption.

Sci Transl Med 2021 01;13(576)

Laboratory of Molecular Immunology, Rockefeller University, New York, NY 10065, USA.

Type 1 interferons (IFN-I) are potent innate antiviral effectors that constrain HIV-1 transmission. However, harnessing these cytokines for HIV-1 cure strategies has been hampered by an incomplete understanding of their antiviral activities at later stages of infection. Here, we characterized the IFN-I sensitivity of 500 clonally derived HIV-1 isolates from the plasma and CD4 T cells of 26 individuals sampled longitudinally after transmission or after antiretroviral therapy (ART) and analytical treatment interruption. We determined the concentration of IFNα2 and IFNβ that reduced viral replication in vitro by 50% (IC) and found consistent changes in the sensitivity of HIV-1 to IFN-I inhibition both across individuals and over time. Resistance of HIV-1 isolates to IFN-I was uniformly high during acute infection, decreased in all individuals in the first year after infection, was reacquired concomitant with CD4 T cell loss, and remained elevated in individuals with accelerated disease. HIV-1 isolates obtained by viral outgrowth during suppressive ART were relatively IFN-I sensitive, resembling viruses circulating just before ART initiation. However, viruses that rebounded after treatment interruption displayed the highest degree of IFNα2 and IFNβ resistance observed at any time during the infection course. These findings indicate a dynamic interplay between host innate responses and the evolving HIV-1 quasispecies, with the relative contribution of IFN-I to HIV-1 control affected by both ART and analytical treatment interruption. Although elevated at transmission, host innate pressures are the highest during viral rebound, limiting the viruses that successfully become reactivated from latency to those that are IFN-I resistant.
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http://dx.doi.org/10.1126/scitranslmed.abd8179DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7923595PMC
January 2021

Recapitulation of HIV-1 Env-antibody coevolution in macaques leading to neutralization breadth.

Science 2021 01 19;371(6525). Epub 2020 Nov 19.

Departments of Medicine and Microbiology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA.

Neutralizing antibodies elicited by HIV-1 coevolve with viral envelope proteins (Env) in distinctive patterns, in some cases acquiring substantial breadth. We report that primary HIV-1 envelope proteins-when expressed by simian-human immunodeficiency viruses in rhesus macaques-elicited patterns of Env-antibody coevolution very similar to those in humans, including conserved immunogenetic, structural, and chemical solutions to epitope recognition and precise Env-amino acid substitutions, insertions, and deletions leading to virus persistence. The structure of one rhesus antibody, capable of neutralizing 49% of a 208-strain panel, revealed a V2 apex mode of recognition like that of human broadly neutralizing antibodies (bNAbs) PGT145 and PCT64-35S. Another rhesus antibody bound the CD4 binding site by CD4 mimicry, mirroring human bNAbs 8ANC131, CH235, and VRC01. Virus-antibody coevolution in macaques can thus recapitulate developmental features of human bNAbs, thereby guiding HIV-1 immunogen design.
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http://dx.doi.org/10.1126/science.abd2638DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8040783PMC
January 2021

Discovery and characterization of novel trans-spliced products of human polyoma JC virus late transcripts from PML patients.

J Cell Physiol 2018 05 18;233(5):4137-4155. Epub 2017 Dec 18.

Laboratory of Molecular Neurovirology, Department of Neuroscience, Lewis Katz School of Medicine at Temple University, Philadelphia, Pennsylvania.

Although the human neurotropic polyomavirus, JC virus (JCV), was isolated almost a half century ago, understanding the molecular mechanisms governing its biology remains highly elusive. JCV infects oligodendrocytes and astrocytes in the central nervous system (CNS) and causes a rare fatal brain disease known as progressive multifocal leukoencephalopathy (PML) in immunocompromised individuals including AIDS. It has a small circular DNA genome (∼5 kb) and generates two primary transcripts from its early and late coding regions, producing several predicted alternatively spliced products mainly by cis-splicing. Here, we report the discovery and characterization of two novel open reading frames (ORF1 and ORF2) associated with JCV late transcripts, generated by an unusual splicing process called trans-splicing. These ORFs result from (i) the trans-splicing of two different lengths of the 5'-short coding region of VP1 between the coding regions of agnoprotein and VP2 after replacing the intron located between these two coding regions and (ii) frame-shifts occurring within the VP2 coding sequences terminated by a stop codon. ORF1 and ORF2 are capable of encoding 58 and 72 aa long proteins respectively and are expressed in infected cells and PML patients. Each ORF protein shares a common coding region with VP1 and has a unique coding sequence of their own. When the expression of the unique coding regions of ORFs is blocked by a stop codon insertion in the viral background, the mutant virus replicates less efficiently when compared to wild-type, suggesting that the newly discovered ORFs play critical roles in the JCV life cycle.
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http://dx.doi.org/10.1002/jcp.26219DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5805571PMC
May 2018