- Philadelphia, Pennsylvania, United States
Jerry Learn
University of Pennsylvania, Medical School, Department Member
Research Interests:
Despite the recent development of highly effective anti-hepatitis C virus (HCV) drugs, the global burden of this pathogen remains immense. Control or eradication of HCV will likely require the broad application of antiviral drugs and... more
Despite the recent development of highly effective anti-hepatitis C virus (HCV) drugs, the global burden of this pathogen remains immense. Control or eradication of HCV will likely require the broad application of antiviral drugs and development of an effective vaccine. A precise molecular identification of transmitted/founder (T/F) HCV genomes that lead to productive clinical infection could play a critical role in vaccine research, as it has for HIV-1. However, the replication schema of these two RNA viruses differ substantially, as do viral responses to innate and adaptive host defenses. These differences raise questions as to the certainty of T/F HCV genome inferences, particularly in cases where multiple closely related sequence lineages have been observed. To clarify these issues and distinguish between competing models of early HCV diversification, we examined seven cases of acute HCV infection in humans and chimpanzees, including three examples of virus transmission between ...
Research Interests: Genetics, Biology, Medicine, Hepatitis C, Coalescent Theory, and 15 moreBiological Sciences, Phylogeny, Humans, Animals, Cluster Analysis, Hepatitis C Virus, Liver Transplantation, Genome, Pan troglodytes, Genotype, Genetic variation, Molecular Sequence Data, Sequence homology, Hepacivirus, and Medical and Health Sciences
asymptomatic HIV type 1-infected patients with relatively high CD41T-cell counts (300 to 450 cells per mm3). Mean values of intrapatient gag nucleotide variation obtained by pairwise comparisons ranged from 0.55 to 2.86%. For three... more
asymptomatic HIV type 1-infected patients with relatively high CD41T-cell counts (300 to 450 cells per mm3). Mean values of intrapatient gag nucleotide variation obtained by pairwise comparisons ranged from 0.55 to 2.86%. For three subjects, this value was equivalent to that reported for intrapatient full-lengthenvvariation. The greatest range of intrapatient mean nucleotide variation for individual protein-coding regions was ob- served
Research Interests:
Research Interests: Genetics, Microbiology, Immunology, Heterosexuality, Molecular Evolution, and 15 moreMedical Microbiology, Biology, Molecular virology, Medicine, HIV, Disease Outbreaks, Humans, Male, Men who have Sex with Men, Molecular cloning, Hiv Aids, Genetic Recombination, Genetic variation, HIV infections, and mononuclear cell
ABSTRACTHuman immunodeficiency virus type 1 (HIV-1) is a difficult target for vaccine development, in part because of its ever-expanding genetic diversity and attendant capacity to escape immunologic recognition. Vaccine efficacy might be... more
ABSTRACTHuman immunodeficiency virus type 1 (HIV-1) is a difficult target for vaccine development, in part because of its ever-expanding genetic diversity and attendant capacity to escape immunologic recognition. Vaccine efficacy might be improved by maximizing immunogen antigenic similarity to viruses likely to be encountered by vaccinees. To this end, we designed a prototype HIV-1 envelope vaccine using a deduced ancestral state for theenvgene. The ancestral state reconstruction method was shown to be >95% accurate by computer simulation and 99.8% accurate when estimating the known inoculum used in an experimental infection study in rhesus macaques. Furthermore, the deduced ancestor gene differed from the set of sequences used to derive the ancestor by an average of 12.3%, while these latter sequences were an average of 17.3% different from each other. A full-length ancestral subtype B HIV-1envgene was constructed and shown to produce a glycoprotein of 160 kDa that bound and fu...
Research Interests: Biology, Virology, Medicine, HIV, Biological Sciences, and 15 morePhylogeny, Virus, Animals, Immunization, Solubility, Human immunodeficiency virus, Antibody, Rabbits, Amino Acid Sequence, Recombinant Proteins, Neutralization, Neutralizing antibodies, Molecular Sequence Data, Neutralization tests, and Medical and Health Sciences
End-stage simian immunodeficiency virus (SIV) isolates are suggested to be the most fit of the evolved virulent variants that precipitate the progression to AIDS. To determine if there were common characteristics of end-stage variants... more
End-stage simian immunodeficiency virus (SIV) isolates are suggested to be the most fit of the evolved virulent variants that precipitate the progression to AIDS. To determine if there were common characteristics of end-stage variants which emerge from accelerated cases of AIDS, a molecular clone was derived directly from serum following in vivo selection of a highly virulent SIV isolate obtained by serial end-stage passage in rhesus monkeys ( Macaca mulatta ). This dominant variant caused a marked cytopathic effect and replicated to very high levels in activated but not resting peripheral blood lymphocytes. Furthermore, although this clone infected but did not replicate to detectable levels in rhesus monocyte-derived macrophages, these cells were able to transmit infection to autologous T cells upon contact. Interestingly, although at low doses this end-stage variant did not use any of the known coreceptors except CCR5, it was able to infect and replicate in human peripheral blood ...
Research Interests: Genetics, Biology, Virology, Medicine, Biological Sciences, and 15 moreVirulence, Phylogeny, Humans, Low Dose, Virus, Animals, Peripheral blood lymphocyte, Molecular cloning, Rhesus Monkey, Macaca Mulatta, Simian Immunodeficiency Virus, Amino Acid Sequence, Severe combined immunodeficiency, Molecular Sequence Data, and Medical and Health Sciences
Currently available simian immunodeficiency virus (SIV) infectious molecular clones (IMCs) and isolates used in non-human primate (NHP) models of AIDS were originally derived from infected macaques during chronic infection or end stage... more
Currently available simian immunodeficiency virus (SIV) infectious molecular clones (IMCs) and isolates used in non-human primate (NHP) models of AIDS were originally derived from infected macaques during chronic infection or end stage disease and may not authentically recapitulate features of transmitted/founder (T/F) genomes that are of particular interest in transmission, pathogenesis, prevention, and treatment studies. We therefore generated and characterized T/F IMCs from genetically and biologically heterogeneous challenge stocks of SIVmac251 and SIVsmE660. Single genome amplification (SGA) was used to identify full-length T/F genomes present in plasma during acute infection resulting from atraumatic rectal inoculation of Indian rhesus macaques with low doses of SIVmac251 or SIVsmE660. All 8 T/F clones yielded viruses that were infectious and replication competent in vitro, with replication kinetics similar to the widely-used chronic-infection derived IMCs SIVmac239 and SIVsmE...
Research Interests:
Research Interests:
Research Interests: Engineering, Evolutionary Biology, Physics, Chemistry, Computational Biology, and 15 moreBiology, Infectious Diseases, Medicine, Multidisciplinary, HIV, Humans, Proteins, PLoS one, Immune Evasion, Amino Acid Sequence, Enzyme Linked Immunosorbent Assay, Immunogenicity, Human proteome project, epitope, and Gene products nef
Research Interests:
... The most conserved sequences are in single-stranded regions (Wheeler & Honeycutt, 1988). ... Most of the work to date has centered on cultivated species and is reviewed in Appels & Honeycutt (1986). Here we look at levels of... more
... The most conserved sequences are in single-stranded regions (Wheeler & Honeycutt, 1988). ... Most of the work to date has centered on cultivated species and is reviewed in Appels & Honeycutt (1986). Here we look at levels of variation in natural, noncultivated plant species.. ...
Research Interests:
Human immunodeficiency virus type 1 (HIV-1) mutations that confer escape from cytotoxic T-lymphocyte (CTL) recognition can sometimes result in lower viral fitness. These mutations can then revert upon transmission to a new host in the... more
Human immunodeficiency virus type 1 (HIV-1) mutations that confer escape from cytotoxic T-lymphocyte (CTL) recognition can sometimes result in lower viral fitness. These mutations can then revert upon transmission to a new host in the absence of CTL-mediated immune selection pressure restricted by the HLA alleles of the prior host. To identify these potentially critical recognition points on the virus, we assessed HLA-driven viral evolution using three phylogenetic correction methods across full HIV-1 subtype C proteomes from a cohort of 261 South Africans and identified amino acids conferring either susceptibility or resistance to CTLs. A total of 558 CTL-susceptible and -resistant HLA-amino acid associations were identified and organized into 310 immunological sets (groups of individual associations related to a single HLA/epitope combination). Mutations away from seven susceptible residues, including four in Gag, were associated with lower plasma viral-RNA loads ( q < 0.2 [whe...
Research Interests: Molecular Evolution, Biology, Virology, HIV, Biological Sciences, and 14 morePhylogeny, South Africa, Humans, Molecular Phylogenetics and Evolution, South African, Human immunodeficiency virus, Amino Acid Profile, Amino Acid Sequence, Base Sequence, Fitness cost, Viral Load, Molecular Sequence Data, Medical and Health Sciences, and HIV infections
Research Interests:
Research Interests:
immunodeficiency virus sequence databases. Maintaining the integrity of human
Identification of the transmitted/founder virus makes possible, for the first time, a genome-wide analysis of host immune responses against the infecting HIV-1 proteome. A complete dissection was made of the primary HIV-1–specific T cell... more
Identification of the transmitted/founder virus makes possible, for the first time, a genome-wide analysis of host immune responses against the infecting HIV-1 proteome. A complete dissection was made of the primary HIV-1–specific T cell response induced in three acutely infected ...