Infection of human T lymphoid cells by human herpesvirus 6 is blocked by two unrelated protein tyrosine kinase inhibitors, biochanin A and herbimycin.
Human herpesvirus 6 is a T lymphotropic herpesvirus that causes exanthem subitum in infants and is considered a potential cofactor in AIDS etiopathogenesis and progression owing to its in vivo and in vitro interactions with human immunodeficiency virus. We report that no differences in phosphorylation on tyrosine residues of cellular proteins were detectable at early times following HHV-6 infection in comparison to uninfected cells. On the contrary, several cellular proteins appeared phosphorylated on tyrosine at 24-48 hr postinfection. In addition, when tyrosine phosphorylation induced by HHV-6 infection was inhibited by the tyrosine kinase inhibitor biochanin A, the infection of HSB-2 cells was also coordinately reduced, as judged by inhibition of cytopathic effect and by inhibition of early and late viral antigen expression. Similar results were obtained with a second unrelated tyrosine kinase inhibitor, herbimycin. The inhibitors seem to act at a late stage of the viral infectious cycle, since neither viral binding nor internalization were affected. Thus, our results indicate that HHV-6 infection leads to the phosphorylation of protein tyrosine kinases, which may play a role in the course of viral infection, probably by participating in the cytopathic effect induced by the virus.
Cirone
M
M
Dipartimento di Medicina Sperimentale e Patologia, Università degli Studi La Sapienza, Rome, Italy.
Zompetta
C
C
Tarasi
D
D
Frati
L
L
Faggioni
A
A
D016227:Benzoquinones; D002460:Cell Line; D002478:Cells, Cultured; D004305:Dose-Response Relationship, Drug; D019833:Genistein; D015654:Herpesvirus 6, Human / Q000502:physiology*; D006801:Humans; D007529:Isoflavones / Q000494:pharmacology*; D047029:Lactams, Macrocyclic; D007963:Leukocytes, Mononuclear / Q000166:cytology; D008214:Lymphocytes / Q000166:cytology / Q000378:metabolism* / Q000821:virology; D010766:Phosphorylation / Q000187:drug effects; D011505:Protein-Tyrosine Kinases / Q000037:antagonists & inhibitors*; D011809:Quinones / Q000494:pharmacology*; D017828:Rifabutin / Q000031:analogs & derivatives; D013601:T-Lymphocytes; D014443:Tyrosine / Q000378:metabolism
D016227:Benzoquinones; D007529:Isoflavones; D047029:Lactams, Macrocyclic; D011809:Quinones; D017828:Rifabutin; D014443:Tyrosine; C020754:herbimycin; D019833:Genistein; D011505:Protein-Tyrosine Kinases; C004541:biochanin A