title: Fibrocytes Differ from Macrophages but Can Be Infected with HIV-1.
abstract: Fibrocytes (fibroblastic leukocytes) are recently identified as unique hematopoietic cells with features of both macrophages and fibroblasts. Fibrocytes are known to contribute to the remodeling or fibrosis of various injured tissues. However, their role in viral infection is not fully understood. In this study, we show that differentiated fibrocytes are phenotypically distinguishable from macrophages but can be infected with HIV-1. Importantly, fibrocytes exhibited persistently infected cell-like phenotypes, the degree of which was more apparent than macrophages. The infected fibrocytes produced replication-competent HIV-1, but expressed HIV-1 mRNA at low levels and strongly resisted HIV-1-induced cell death, which enabled them to support an extremely long-term HIV-1 production at low but steady levels. More importantly, our results suggested that fibrocytes were susceptible to HIV-1 regardless of their differentiation state, in contrast to the fact that monocytes become susceptible to HIV-1 after the differentiation into macrophages. Our findings indicate that fibrocytes are the previously unreported HIV-1 host cells, and they suggest the importance of considering fibrocytes as one of the long-lived persistently infected cells for curing HIV-1.
authors.affiliation: Center for AIDS Research, Kumamoto University, Kumamoto 860-0811, Japan; International Research Center for Medical Sciences, Kumamoto University, Kumamoto 860-0811, Japan;
authors.forename: Michihiro
authors.initials: M
authors.lastname: Hashimoto
authors.affiliation: Center for AIDS Research, Kumamoto University, Kumamoto 860-0811, Japan; International Research Center for Medical Sciences, Kumamoto University, Kumamoto 860-0811, Japan;
authors.forename: Hesham
authors.initials: H
authors.lastname: Nasser
authors.affiliation: Center for AIDS Research, Kumamoto University, Kumamoto 860-0811, Japan; International Research Center for Medical Sciences, Kumamoto University, Kumamoto 860-0811, Japan;
authors.forename: Farzana
authors.initials: F
authors.lastname: Bhuyan
authors.affiliation: Center for AIDS Research, Kumamoto University, Kumamoto 860-0811, Japan;
authors.forename: Nozomi
authors.initials: N
authors.lastname: Kuse
authors.affiliation: Center for AIDS Research, Kumamoto University, Kumamoto 860-0811, Japan; International Research Center for Medical Sciences, Kumamoto University, Kumamoto 860-0811, Japan;
authors.forename: Yorifumi
authors.initials: Y
authors.lastname: Satou
authors.affiliation: AIDS Research Center, National Institute of Infectious Diseases, Tokyo 162-8640, Japan;
authors.forename: Shigeyoshi
authors.initials: S
authors.lastname: Harada
authors.affiliation: AIDS Research Center, National Institute of Infectious Diseases, Tokyo 162-8640, Japan;
authors.forename: Kazuhisa
authors.initials: K
authors.lastname: Yoshimura
authors.affiliation: Research Institute for Microbial Diseases, Osaka University, Osaka 565-0871, Japan;
authors.forename: Jun-ichi
authors.initials: J
authors.lastname: Sakuragi
authors.affiliation: Department of Medical Virology, Kumamoto University, Kumamoto 860-8556, Japan;
authors.forename: Kazuaki
authors.initials: K
authors.lastname: Monde
authors.affiliation: Department of Medical Virology, Kumamoto University, Kumamoto 860-8556, Japan;
authors.forename: Yosuke
authors.initials: Y
authors.lastname: Maeda
authors.affiliation: National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892; and.
authors.forename: Sarah
authors.initials: S
authors.lastname: Welbourn
authors.affiliation: National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892; and.
authors.forename: Klaus
authors.initials: K
authors.lastname: Strebel
authors.affiliation: Center for AIDS Research, Kumamoto University, Kumamoto 860-0811, Japan; International Research Center for Medical Sciences, Kumamoto University, Kumamoto 860-0811, Japan;
authors.forename: Ekram W
authors.initials: EW
authors.lastname: Abd El-Wahab
authors.affiliation: Center for AIDS Research, Kumamoto University, Kumamoto 860-0811, Japan; International Research Center for Medical Sciences, Kumamoto University, Kumamoto 860-0811, Japan;
authors.forename: Mitsue
authors.initials: M
authors.lastname: Miyazaki
authors.affiliation: Center for AIDS Research, Kumamoto University, Kumamoto 860-0811, Japan;
authors.forename: Shinichiro
authors.initials: S
authors.lastname: Hattori
authors.affiliation: Center for AIDS Research, Kumamoto University, Kumamoto 860-0811, Japan;
authors.forename: Nopporn
authors.initials: N
authors.lastname: Chutiwitoonchai
authors.affiliation: Center for AIDS Research, Kumamoto University, Kumamoto 860-0811, Japan;
authors.forename: Masateru
authors.initials: M
authors.lastname: Hiyoshi
authors.affiliation: AIDS Clinical Center, National Center for Global Health and Medicine, Tokyo 162-0052, Japan.
authors.forename: Shinichi
authors.initials: S
authors.lastname: Oka
authors.affiliation: Center for AIDS Research, Kumamoto University, Kumamoto 860-0811, Japan; International Research Center for Medical Sciences, Kumamoto University, Kumamoto 860-0811, Japan;
authors.forename: Masafumi
authors.initials: M
authors.lastname: Takiguchi
authors.affiliation: Center for AIDS Research, Kumamoto University, Kumamoto 860-0811, Japan; International Research Center for Medical Sciences, Kumamoto University, Kumamoto 860-0811, Japan; ssuzu06@kumamoto-u.ac.jp.
authors.forename: Shinya
authors.initials: S
authors.lastname: Suzu
mesh_terms: D048430:Cell Shape / Q000235:genetics; D002478:Cells, Cultured; D005347:Fibroblasts / Q000166:cytology / Q000378:metabolism / Q000821:virology*; D015967:Gene Expression Regulation, Viral; D015658:HIV Infections / Q000097:blood; D015497:HIV-1 / Q000235:genetics / Q000502:physiology*; D054884:Host-Pathogen Interactions / Q000235:genetics; D006801:Humans; D007962:Leukocytes / Q000166:cytology / Q000378:metabolism / Q000821:virology*; D008264:Macrophages / Q000166:cytology / Q000378:metabolism / Q000821:virology*; D018613:Microscopy, Confocal; D009000:Monocytes / Q000166:cytology / Q000378:metabolism / Q000821:virology; D020411:Oligonucleotide Array Sequence Analysis; D010641:Phenotype; D059467:Transcriptome; D014779:Virus Replication / Q000235:genetics