Inhibition of herpes simplex virus replication by retinoic acid.
The retinoic acid (RA) isomers all-trans-RA, 9-cis-RA and 13-cis-RA as well as other retinoids were tested for their ability to reduce the yield of herpes simplex virus-1 (HSV-1). RA isomers reduced HSV-1 replication whereas the other retinoids, retinol, retinal, beta-carotene and amide derivatives of RA were not inhibitory. All-trans-RA reduced the yield of HSV-1 by 100-fold at 5 micrograms/ml but 9-cis-RA and 13-cis-RA reduced viral replication by 10-fold. At a concentration of 10 micrograms/ml all-trans-RA and 9-cis-RA reduced virus yield by 1000-fold while 13-cis-RA decreased HSV-1 production by 100-fold. RA isomers at a concentration of 10 micrograms/ml were not cytotoxic for the Vero cells used in these studies. Immunofluorescence studies showed that all-trans-RA treated cell cultures exhibited small foci of virus specific immunostaining while untreated cultures displayed intense HSV-1 immunoreactivity in virtually the entire cell population. RA-dependent inhibition of HSV-1 replication required the presence of RA with the virus. HSV-1 replication proceeded when RA was removed from infected cells. Treatment of cell cultures with RA did not induce gene expression for type-1 interferon (IFN) or for the type-1 IFN inducible genes studied suggesting that RA inhibition of HSV-1 replication is not mediated by IFN. These studies have established the ability of RA to reduce the replication of HSV-1 in vitro.
Isaacs
C E
CE
Department of Developmental Biochemistry, New York State Institute for Basic Research, Staten Island 10314, USA.
Kascsak
R
R
Pullarkat
R K
RK
Xu
W
W
Schneidman
K
K
D000077556:Alitretinoin; D000818:Animals; D000998:Antiviral Agents / Q000494:pharmacology*; D002522:Chlorocebus aethiops; D019084:Fluorescent Antibody Technique, Indirect; D006367:HeLa Cells; D018259:Herpesvirus 1, Human / Q000187:drug effects* / Q000254:growth & development / Q000502:physiology; D006801:Humans; D016898:Interferon-alpha / Q000235:genetics / Q000378:metabolism; D016899:Interferon-beta / Q000235:genetics / Q000378:metabolism; D015474:Isotretinoin / Q000494:pharmacology; D012333:RNA, Messenger; D014212:Tretinoin / Q000494:pharmacology*; D014709:Vero Cells; D014779:Virus Replication / Q000187:drug effects
D000998:Antiviral Agents; D016898:Interferon-alpha; D012333:RNA, Messenger; D000077556:Alitretinoin; D014212:Tretinoin; D016899:Interferon-beta; D015474:Isotretinoin