Cross-Species Rhesus Cytomegalovirus Infection of Cynomolgus Macaques
Publication Date
November 09, 2016
Authors
Benjamin J. Burwitz, Daniel Malouli, Benjamin N. Bimber, Jason S. Reed, et al
Volume
12
Issue
11
Pages
e1006014
DOI
https://dx.plos.org/10.1371/journal.ppat.1006014
Publisher URL
http://journals.plos.org/plospathogens/article?id=10.1371%2Fjournal.ppat.1006014
Scopus
85002271187
Mendeley
http://www.mendeley.com/research/crossspecies-rhesus-cytomegalovirus-infection-cynomolgus-macaques
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Mendeley | Further Information

{"title"=>"Cross-Species Rhesus Cytomegalovirus Infection of Cynomolgus Macaques", "type"=>"journal", "authors"=>[{"first_name"=>"Benjamin J.", "last_name"=>"Burwitz", "scopus_author_id"=>"15831128700"}, {"first_name"=>"Daniel", "last_name"=>"Malouli", "scopus_author_id"=>"24503757000"}, {"first_name"=>"Benjamin N.", "last_name"=>"Bimber", "scopus_author_id"=>"14053443700"}, {"first_name"=>"Jason S.", "last_name"=>"Reed", "scopus_author_id"=>"7403642174"}, {"first_name"=>"Abigail B.", "last_name"=>"Ventura", "scopus_author_id"=>"36088372600"}, {"first_name"=>"Meaghan H.", "last_name"=>"Hancock", "scopus_author_id"=>"56343185100"}, {"first_name"=>"Luke S.", "last_name"=>"Uebelhoer", "scopus_author_id"=>"25121870900"}, {"first_name"=>"Amruta", "last_name"=>"Bhusari", "scopus_author_id"=>"26427924000"}, {"first_name"=>"Katherine B.", "last_name"=>"Hammond", "scopus_author_id"=>"55735287900"}, {"first_name"=>"Renee G.", "last_name"=>"Espinosa Trethewy", "scopus_author_id"=>"57192252062"}, {"first_name"=>"Alex", "last_name"=>"Klug", "scopus_author_id"=>"57192240006"}, {"first_name"=>"Alfred W.", "last_name"=>"Legasse", "scopus_author_id"=>"14018193800"}, {"first_name"=>"Michael K.", "last_name"=>"Axthelm", "scopus_author_id"=>"7004004818"}, {"first_name"=>"Jay A.", "last_name"=>"Nelson", "scopus_author_id"=>"35461231000"}, {"first_name"=>"Byung S.", "last_name"=>"Park", "scopus_author_id"=>"7402834719"}, {"first_name"=>"Daniel N.", "last_name"=>"Streblow", "scopus_author_id"=>"6603615291"}, {"first_name"=>"Scott G.", "last_name"=>"Hansen", "scopus_author_id"=>"7403079839"}, {"first_name"=>"Louis J.", "last_name"=>"Picker", "scopus_author_id"=>"7005304033"}, {"first_name"=>"Klaus", "last_name"=>"Früh", "scopus_author_id"=>"7004554649"}, {"first_name"=>"Jonah B.", "last_name"=>"Sacha", "scopus_author_id"=>"16025548800"}], "year"=>2016, "source"=>"PLoS Pathogens", "identifiers"=>{"scopus"=>"2-s2.0-85002271187", "sgr"=>"85002271187", "issn"=>"15537374", "doi"=>"10.1371/journal.ppat.1006014", "pmid"=>"27829026", "pui"=>"613548239"}, "id"=>"ca557724-882b-3c9d-a34c-d73d683b1c95", "abstract"=>"Cytomegaloviruses (CMV) are highly species-specific due to millennia of co-evolution and adaptation to their host, with no successful experimental cross-species infection in primates reported to date. Accordingly, full genome phylogenetic analysis of multiple new CMV field isolates derived from two closely related nonhuman primate species, Indian-origin rhesus macaques (RM) and Mauritian-origin cynomolgus macaques (MCM), revealed distinct and tight lineage clustering according to the species of origin, with MCM CMV isolates mirroring the limited genetic diversity of their primate host that underwent a population bottleneck 400 years ago. Despite the ability of Rhesus CMV (RhCMV) laboratory strain 68–1 to repli-cate efficiently in MCM fibroblasts and potently inhibit antigen presentation to MCM T cells in vitro, RhCMV 68–1 failed to productively infect MCM in vivo, even in the absence of host CD8+ T and NK cells. In contrast, RhCMV clone 68–1.2, genetically repaired to express the homologues of the HCMV anti-apoptosis gene UL36 and epithelial cell tropism genes UL128 and UL130 absent in 68–1, efficiently infected MCM as evidenced by the induction of transgene-specific T cells and virus shedding. Recombinant variants of RhCMV 68–1 and 68–1.2 revealed that expression of either UL36 or UL128 together with UL130 enabled productive MCM infection, indicating that multiple layers of cross-species restriction oper-ate even between closely related hosts. Cumulatively, these results implicate cell tropism and evasion of apoptosis as critical determinants of CMV transmission across primate spe-cies barriers, and extend the macaque model of human CMV infection and immunology to MCM, a nonhuman primate species with uniquely simplified host immunogenetics.), R21 AI108401 and R01 AI117802 to JBS, and P51 OD011092 to ONPRC (www.nih. gov). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. expand the existing models by isolating new full-length, non-human primate CMV strains that more closely resemble primary HCMV isolates. In addition, we identify determinants needed for recombinant clones of RhCMV to infect MCM both in vitro and in vivo. Given their simplified immunogenetics, these results enable the use of MCM to deepen our understanding of CMV immunology.", "link"=>"http://www.mendeley.com/research/crossspecies-rhesus-cytomegalovirus-infection-cynomolgus-macaques", "reader_count"=>19, "reader_count_by_academic_status"=>{"Unspecified"=>3, "Researcher"=>8, "Student > Ph. D. Student"=>3, "Student > Bachelor"=>3, "Lecturer > Senior Lecturer"=>1, "Professor"=>1}, "reader_count_by_user_role"=>{"Unspecified"=>3, "Researcher"=>8, "Student > Ph. D. Student"=>3, "Student > Bachelor"=>3, "Lecturer > Senior Lecturer"=>1, "Professor"=>1}, "reader_count_by_subject_area"=>{"Unspecified"=>3, "Biochemistry, Genetics and Molecular Biology"=>5, "Agricultural and Biological Sciences"=>2, "Medicine and Dentistry"=>5, "Pharmacology, Toxicology and Pharmaceutical Science"=>1, "Immunology and Microbiology"=>3}, "reader_count_by_subdiscipline"=>{"Medicine and Dentistry"=>{"Medicine and Dentistry"=>5}, "Immunology and Microbiology"=>{"Immunology and Microbiology"=>3}, "Agricultural and Biological Sciences"=>{"Agricultural and Biological Sciences"=>2}, "Biochemistry, Genetics and Molecular Biology"=>{"Biochemistry, Genetics and Molecular Biology"=>5}, "Unspecified"=>{"Unspecified"=>3}, "Pharmacology, Toxicology and Pharmaceutical Science"=>{"Pharmacology, Toxicology and Pharmaceutical Science"=>1}}, "group_count"=>1}

Scopus | Further Information

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