title: Peripheral blood neutrophils from hepatitis C virus-infected patients are replication sites of the virus.
abstract: OBJECTIVE
  Hepatitis C virus (HCV) is able to cause not only acute and chronic liver disease, but also immunologic and hematologic disorders. In order to clarify the extra-hepatic tropism of HCV, and to understand the pathogenetic mechanisms of HCV infection, we evaluated viral replication in peripheral blood mononuclear cells.
  
  
  METHODS
  The presence of genomic and antigenomic (replicative) forms of HCV in B- and T-lymphocytes, monocytes, and polymorphonuclear leukocytes (PML) was determined by reverse transcriptase-polymerase chain reaction in 54 HCV-RNA positive patients and, as control groups, in 10 patients who had recovered from HCV infection without evidence of serum HCV-RNA, and in 10 HCV-negative subjects.
  
  
  RESULTS
  In HCV-RNA positive patients, the genomic RNA was found in 94% of B-cells, in 14% of T-cells, in 40% of monocytes and in 77% of PML, while only 1 of the HCV-RNA negative subjects showed positivity in B-cells. The anti-genomic form of HCV-RNA was found in 52% of B-cells, in 3% of monocytes, and in 31% of PML. By contrast, it was never detected in T-cells and in HCV-RNA negative subjects. Neither genomic nor anti-genomic forms were found in HCV-negative cases.
  
  
  CONCLUSIONS
  These data suggest that PML are replication sites of HCV. Whether the infection occurs at the level of the stem cells or subsequently during myeloid cell differentiation is, as yet, unknown. The absence of correlation between the presence of replicative forms and any clinical and/or laboratory data opens the question of the role of HCV replication in extra-hepatic sites.
authors.affiliation: Department of Microbiology and Immunology; Pordenone General Hospital, Pordenone, Italy.
authors.forename: M
authors.initials: M
authors.lastname: Crovatto
authors.forename: G
authors.initials: G
authors.lastname: Pozzato
authors.forename: F
authors.initials: F
authors.lastname: Zorat
authors.forename: E
authors.initials: E
authors.lastname: Pussini
authors.forename: F
authors.initials: F
authors.lastname: Nascimben
authors.forename: S
authors.initials: S
authors.lastname: Baracetti
authors.forename: M G
authors.initials: MG
authors.lastname: Grando
authors.forename: C
authors.initials: C
authors.lastname: Mazzaro
authors.forename: M
authors.initials: M
authors.lastname: Reitano
authors.forename: M L
authors.initials: ML
authors.lastname: Modolo
authors.forename: P
authors.initials: P
authors.lastname: Martelli
authors.forename: A
authors.initials: A
authors.lastname: Spada
authors.forename: G
authors.initials: G
authors.lastname: Santini
mesh_terms: D000328:Adult; D000368:Aged; D001402:B-Lymphocytes / Q000821:virology; D005260:Female; D016174:Hepacivirus / Q000235:genetics / Q000254:growth & development*; D006526:Hepatitis C / Q000097:blood / Q000821:virology*; D006801:Humans; D008297:Male; D008875:Middle Aged; D009000:Monocytes / Q000821:virology; D009504:Neutrophils / Q000821:virology*; D012367:RNA, Viral / Q000097:blood; D013601:T-Lymphocytes / Q000821:virology; D014775:Virus Activation; D014779:Virus Replication
chemical_list: D012367:RNA, Viral