In vitro selection of human cytomegalovirus variants unable to transfer virus and virus products from infected cells to polymorphonuclear leukocytes and to grow in endothelial cells.
Four human cytomegalovirus (HCMV) isolates from different clinical sources were extensively propagated in human embryonic lung fibroblasts (HELF). Plaque isolates from each of the four virus strains were evaluated for their ability to be transferred to polymorphonuclear leukocytes (PMNL) and to grow in endothelial cells (EC). While all four of the clinical strains were found to be both PMNL- and EC-tropic, variants were identified from each of the four strains that lacked both biological properties, while three of the four parental strains lost their transfer capacity before passage 50 in HELF. It was demonstrated that one of the four field isolates (VR6110) and its transfer-deficient variant were genetically related, but showed different curves of virus yield in HELF. In addition, neither the immediate-early (IE) mRNA nor the IE protein p72 were found to be transferred to PMNL before 72 h post-infection (late in infection) or in the presence of viral DNA replication inhibitors. These findings link EC and PMNL tropism and suggest that PMNL tropism is a late HCMV function.
Grazia Revello
M
M
Servizio di Virologia, Istituto di Ricovero e Cura a Carattere Scientifico Policlinico San Matteo, 27100 Pavia, Italy1.
Baldanti
Fausto
F
Servizio di Virologia, Istituto di Ricovero e Cura a Carattere Scientifico Policlinico San Matteo, 27100 Pavia, Italy1.
Percivalle
Elena
E
Servizio di Virologia, Istituto di Ricovero e Cura a Carattere Scientifico Policlinico San Matteo, 27100 Pavia, Italy1.
Sarasini
Antonella
A
Servizio di Virologia, Istituto di Ricovero e Cura a Carattere Scientifico Policlinico San Matteo, 27100 Pavia, Italy1.
De-Giuli
Luciana
L
Servizio di Virologia, Istituto di Ricovero e Cura a Carattere Scientifico Policlinico San Matteo, 27100 Pavia, Italy1.
Genini
Emilia
E
Servizio di Virologia, Istituto di Ricovero e Cura a Carattere Scientifico Policlinico San Matteo, 27100 Pavia, Italy1.
Lilleri
Daniele
D
Servizio di Virologia, Istituto di Ricovero e Cura a Carattere Scientifico Policlinico San Matteo, 27100 Pavia, Italy1.
Labò
Nazarena
N
Servizio di Virologia, Istituto di Ricovero e Cura a Carattere Scientifico Policlinico San Matteo, 27100 Pavia, Italy1.
Gerna
Giuseppe
G
Servizio di Virologia, Istituto di Ricovero e Cura a Carattere Scientifico Policlinico San Matteo, 27100 Pavia, Italy1.
D015139:Blotting, Southern; D002460:Cell Line; D018920:Coculture Techniques; D003587:Cytomegalovirus / Q000235:genetics* / Q000254:growth & development / Q000502:physiology*; D004730:Endothelium, Vascular / Q000166:cytology / Q000821:virology*; D005347:Fibroblasts; D017781:Genes, Immediate-Early / Q000235:genetics; D014644:Genetic Variation / Q000235:genetics; D006801:Humans; D007700:Kinetics; D008168:Lung; D009154:Mutation / Q000235:genetics; D009504:Neutrophils / Q000166:cytology / Q000378:metabolism* / Q000821:virology*; D009928:Organ Specificity; D012150:Polymorphism, Restriction Fragment Length; D012641:Selection, Genetic; D012692:Serial Passage; D019562:Viral Load; D014764:Viral Proteins / Q000378:metabolism; D014779:Virus Replication
D014764:Viral Proteins