Effect of serum and CTL on focal growth of human cytomegalovirus.
BACKGROUND
In immunocompromised patients only cytotoxic T-lymphocytes (CTL) but not antiviral antibodies appear to be efficient in control of human cytomegalovirus (HCMV) infection. This is contrasted by the well-documented neutralising activity of patient sera against standard HCMV strains.


OBJECTIVE
We tested the hypothesis that a cell-culture model based on a recent clinical HCMV isolate would more accurately approximate the clinical situation and provide an explanation for the failure of neutralising antibodies in efficient restriction of HCMV infection.


METHODS
Sera from five bone marrow transplant recipients with or without prolonged HCMV replication were analysed by an enzyme-linked immunoassay for their capacity to neutralise cell-free HCMV preparations. The inhibitory effect of these sera on viral cell-to-cell-spread was then quantified by focus expansion assays using a recent clinical HCMV-isolate and was finally compared to the inhibitory effect of HCMV-specific CTL lines.


RESULTS
Prolonged HCMV replication occurred in three patients despite high titres of neutralising antibodies. In contrast to the strong inhibitory effect on cell-free HCMV, their sera could not inhibit the focal growth of a recent cell-associated HCMV isolate, whereas CTL clones directed against pUL123 or pUL83 of HCMV effectively limited focal expansion of the clinical isolate in fibroblast culture.


CONCLUSIONS
Focus expansion assays based on a cell-associated clinical HCMV isolate provide a model for the in vivo effectiveness of virus-specific CTL and neutralising antibodies. Our data support the assumption that due to their strict cell-association clinical HCMV strains are withdrawn from neutralising antibodies.
Sinzger
Christian
C
Institute of Medical Virology, University of Tuebingen, Tuebingen, Germany. christian.sinzger@med.uni-tuebingen.de
Mangin
Martina
M
Weinstock
Christof
C
Topp
Max S
MS
Hebart
Holger
H
Einsele
Hermann
H
Jahn
Gerhard
G
D000914:Antibodies, Viral / Q000097:blood / Q000276:immunology; D016026:Bone Marrow Transplantation / Q000276:immunology; D003587:Cytomegalovirus / Q000254:growth & development / Q000276:immunology* / Q000502:physiology; D003586:Cytomegalovirus Infections / Q000097:blood / Q000276:immunology* / Q000821:virology; D015234:HLA-A Antigens / Q000276:immunology; D015789:HLA-A2 Antigen; D006801:Humans; D007106:Immune Sera / Q000276:immunology; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology*; D017361:Viral Nonstructural Proteins / Q000276:immunology; D015678:Viral Structural Proteins / Q000276:immunology; D014779:Virus Replication
D000914:Antibodies, Viral; D015234:HLA-A Antigens; C435939:HLA-A*02:01 antigen; D015789:HLA-A2 Antigen; D007106:Immune Sera; D017361:Viral Nonstructural Proteins; D015678:Viral Structural Proteins