Cross-talk between human herpesvirus 8 and the transactivator protein in the pathogenesis of Kaposi's sarcoma in HIV-infected patients.
AIDS-associated Kaposi's sarcoma (AKS) is particularly aggressive and it is one of the principal neoplasms in regions of Africa affected by both high endemic HHV8 and epidemic HIV infection. In this study, serum samples from 18 patients with Kaposi's sarcoma from Tanzania, mostly males (n = 15 vs 3), were subjected to analysis with respect to HHV8-DNA load and antibody spectrum against the HIV-1 tat protein. Of the 18 patients, 14 were HIV-1-positive. The median HHV8 virus load in the HIV-1-positive group was 2075 DNA copies/ml, compared to 450 copies/ml in the HIV-1-negative group. In the HIV-1-positive group, the males had a higher HHV8-DNA virus load as compared to females (median: 4600 vs 1400 genome copies per ml). Since tat can promote AKS development (4-6) by intercellular signalling pathways, and these signals can be abolished by anti-tat IgG (7-9), we have examined the anti-tat IgG spectrum in this study. It would be expected that the levels of serum HHV8-DNA are higher in KS patients who have low anti-tat IgG titer, or who are anti-tat IgG-negative. In the present study, seven out of fifteen AKS patients were positive for anti-tat IgG. Although, we have not seen a strict quantitative relationship between serum anti-tat IgG and HHV8-DNA levels, our data appear to suggest a correlation between the two parameters. In view of these observations and the published data, we suggest that cross-signalling pathways between the tat protein and HHV8-DNA are involved in the complexity of pathogenesis of Kaposi's sarcoma.
Chandra
Angelika
A
Institute of Medical Virology, Institute of Transfusion Medicine, Frankfurt University Medical School, 60590 Frankfurt, Germany.
Demirhan
Ilhan
I
Massambu
Charles
C
Pyakurel
Pawan
P
Kaaya
Ephata
E
Enbom
Malin
M
Urassa
Willy
W
Linde
Annika
A
Heiden
Thomas
T
Biberfeld
Peter
P
Doerr
Hans W
HW
Cinatl
J
J
Loewer
Johannes
J
Chandra
Prakash
P
D000328:Adult; D000368:Aged; D002648:Child; D004279:DNA, Viral / Q000097:blood; D005260:Female; D015694:Gene Products, rev / Q000276:immunology / Q000502:physiology*; D015483:HIV Antibodies / Q000097:blood; D015658:HIV Infections / Q000097:blood / Q000821:virology*; D015497:HIV-1; D019288:Herpesvirus 8, Human / Q000235:genetics / Q000502:physiology*; D006801:Humans; D007074:Immunoglobulin G / Q000276:immunology; D008297:Male; D008875:Middle Aged; D012514:Sarcoma, Kaposi / Q000097:blood / Q000821:virology*; D019562:Viral Load; D054321:rev Gene Products, Human Immunodeficiency Virus
D004279:DNA, Viral; D015694:Gene Products, rev; D015483:HIV Antibodies; D007074:Immunoglobulin G; D054321:rev Gene Products, Human Immunodeficiency Virus