title: Genetic Dissection of the Host Tropism of Human-Tropic Pathogens.
abstract: Infectious diseases are the second leading cause of death worldwide. Although the host multitropism of some pathogens has rendered their manipulation possible in animal models, the human-restricted tropism of numerous viruses, bacteria, fungi, and parasites has seriously hampered our understanding of these pathogens. Hence, uncovering the genetic basis underlying the narrow tropism of such pathogens is critical for understanding their mechanisms of infection and pathogenesis. Moreover, such genetic dissection is essential for the generation of permissive animal models that can serve as critical tools for the development of therapeutics or vaccines against challenging human pathogens. In this review, we describe different experimental approaches utilized to uncover the genetic foundation regulating pathogen host tropism as well as their relevance for studying the tropism of several important human pathogens. Finally, we discuss the current and future uses of this knowledge for generating genetically modified animal models permissive for these pathogens.
authors.affiliation: Department of Molecular Biology, Princeton University, Princeton, New Jersey 08544; email: fdouam@princeton.edu , jgaska@princeton.edu , bwiner@princeton.edu , qding@princeton.edu , schaewen@princeton.edu , aploss@princeton.edu.
authors.forename: Florian
authors.initials: F
authors.lastname: Douam
authors.affiliation: Department of Molecular Biology, Princeton University, Princeton, New Jersey 08544; email: fdouam@princeton.edu , jgaska@princeton.edu , bwiner@princeton.edu , qding@princeton.edu , schaewen@princeton.edu , aploss@princeton.edu.
authors.forename: Jenna M
authors.initials: JM
authors.lastname: Gaska
authors.affiliation: Department of Molecular Biology, Princeton University, Princeton, New Jersey 08544; email: fdouam@princeton.edu , jgaska@princeton.edu , bwiner@princeton.edu , qding@princeton.edu , schaewen@princeton.edu , aploss@princeton.edu.
authors.forename: Benjamin Y
authors.initials: BY
authors.lastname: Winer
authors.affiliation: Department of Molecular Biology, Princeton University, Princeton, New Jersey 08544; email: fdouam@princeton.edu , jgaska@princeton.edu , bwiner@princeton.edu , qding@princeton.edu , schaewen@princeton.edu , aploss@princeton.edu.
authors.forename: Qiang
authors.initials: Q
authors.lastname: Ding
authors.affiliation: Department of Molecular Biology, Princeton University, Princeton, New Jersey 08544; email: fdouam@princeton.edu , jgaska@princeton.edu , bwiner@princeton.edu , qding@princeton.edu , schaewen@princeton.edu , aploss@princeton.edu.
authors.forename: Markus
authors.initials: M
authors.lastname: von Schaewen
authors.affiliation: Department of Molecular Biology, Princeton University, Princeton, New Jersey 08544; email: fdouam@princeton.edu , jgaska@princeton.edu , bwiner@princeton.edu , qding@princeton.edu , schaewen@princeton.edu , aploss@princeton.edu.
authors.forename: Alexander
authors.initials: A
authors.lastname: Ploss
mesh_terms: D000222:Adaptation, Physiological / Q000235:genetics; D000818:Animals; D064113:CRISPR-Cas Systems; D004195:Disease Models, Animal; D020869:Gene Expression Profiling / Q000379:methods*; D005818:Genetic Engineering / Q000379:methods; D006238:Haploidy; D058507:Host Specificity / Q000235:genetics*; D054884:Host-Pathogen Interactions / Q000235:genetics*; D006801:Humans; D007113:Immunity, Innate / Q000235:genetics*; D008822:Mice, Transgenic; D018523:Tropism
keywords: animal models; bacteria; genetic engineering; humanized mice; pathogen host tropism; virus