Herpes simplex virus ICP0 and ICP4 immediate early proteins strongly enhance expression of a retrovirus harboured by a leptomeningeal cell line from a patient with multiple sclerosis.
A leptomeningeal cell line (LM7) harbouring an unknown retrovirus was recently isolated from the cerebrospinal fluid of a patient with multiple sclerosis. However, spontaneous expression of the LM7 retrovirus in this primary culture is quite low. We present results showing that in vitro infection of LM7 cells with herpes simplex virus type 1 (HSV-1), but not that of control cells, results in (i) potent stimulation of the specific reverse transcriptase (RT) activity detected in the culture supernatant and (ii) co-expression of both typical HSV-1 virions and abundant retrovirus-like particles. Transfection of LM7 cells with plasmids expressing HSV-1 immediate early (IE) ICP0 and ICP4 proteins produced a similar enhancement of RT activity in culture supernatants with retrovirus-like particles being identifiable by electron microscopy. These effects were not observed with a plasmid expressing ICP27 or with the parental plasmid in LM7 cells, nor with any of these four plasmids in control cells. These results show that HSV IE trans-activating proteins strongly enhance the expression of the latent retrovirus present in LM7 cells. The possible role in vivo of herpesviruses as 'triggering' cofactors in the retrovirus hypothesis for multiple sclerosis aetiology is also discussed.
Perron
H
H
UMR 103 CNRS/Biomérieux, ENSL, Lyon, France.
Suh
M
M
Lalande
B
B
Gratacap
B
B
Laurent
A
A
Stoebner
P
P
Seigneurin
J M
JM
D001099:Arachnoid / Q000166:cytology / Q000382:microbiology; D002460:Cell Line; D006801:Humans; D017874:Immediate-Early Proteins; D009103:Multiple Sclerosis / Q000382:microbiology*; D010841:Pia Mater / Q000166:cytology / Q000382:microbiology; D010957:Plasmids; D012194:RNA-Directed DNA Polymerase / Q000378:metabolism*; D012190:Retroviridae / Q000302:isolation & purification / Q000378:metabolism*; D012191:Retroviridae Proteins / Q000096:biosynthesis*; D018139:Simplexvirus / Q000502:physiology*; D014162:Transfection; D044767:Ubiquitin-Protein Ligases; D014764:Viral Proteins / Q000502:physiology*; D054334:Viral Regulatory and Accessory Proteins / Q000502:physiology*
D017874:Immediate-Early Proteins; D012191:Retroviridae Proteins; D014764:Viral Proteins; D054334:Viral Regulatory and Accessory Proteins; C048925:herpes simplex virus, type 1 protein ICP4; D044767:Ubiquitin-Protein Ligases; C051804:Vmw110 protein, Human herpesvirus 1; D012194:RNA-Directed DNA Polymerase