Human herpesvirus 6 in hematologic diseases in China.

BACKGROUND AND OBJECTIVE: The prevalence and pathogenic role of human herpesvirus 6 (HHV-6) in various benign and malignant hematologic diseases remain largely unknown. The aim of this study was to search for a possible involvement of HHV-6 in the pathogenesis of hematologic diseases. DESIGN AND METHODS: The presence of HHV-6 DNA sequences was examined by polymerase chain reaction (PCR) in bone marrow mononuclear cells from 241 patients with benign and malignant hematologic diseases in China. Platelet-associated immunoglobulin (PAIg) of 66 idiopathic thrombocytopenic purpura (ITP) patients was measured by competitive enzyme-linked immunosorbent assay. The presence of HHV-6 DNA in sera from 31 ITP patients was examined by PCR. Paired serum samples from 19 ITP patients were analyzed for anti-HHV-6 IgG titers using an indirect immunofluorescence assay. RESULTS: HHV-6 DNA was detected in 41% and 37.5% of ITP and acute leukemia patients respectively, but in only 6.7% of patients with iron deficiency anemia. HHV-6 positivity for ITP patients with excessive PAIgG was significantly higher than in patients with a normal level of PAIgG. HHV-6 DNA was not detected in any of the serum samples from ITP patients. None of the 19 cases of ITP showed a significant increase in anti-HHV-6 antibody titers during the convalescent phase compared with the onset phase. INTERPRETATION AND CONCLUSIONS: Our results indicate that HHV-6 infection might be associated with excessive PAIgG in some cases of ITP, and that the virus persists in a latent state. The pathogenic role of HHV-6 in ITP needs to be confirmed by further investigations.

[An etiology study on the 1986 epidemic of acute hemorrhagic conjunctivitis in China].

An epidemic of Acute Hemorrhagic Conjunctivitis (AHC) broke out in Shanghai, Henan and Fujian provinces of China in 1986. Twenty four strains of etiologically suspected virus were then isolated but not correctly identified. In 1990 9 out of 24 strains from these three places were re-examined by us in our laboratory, and found feasible to be neutralized by CA 24V antiserum, but not by antiserum to EV 70 as once reported by Henan. It was also found that these viruses (one strain from each of these three places) produced pathogenic changes in suckling mice, showed definite immuno-fluorescence with Mcabs, and were neutralized by McAbs against CA 24V which was isolated from Beijing by our laboratory in 1988. It is evident that all the isolates isolated from Shanghai, Henan and Fujian provinces in 1986 were Coxsackie-virus A 24 variant (CA 24V).

Phylogenetic analysis of a coxsackievirus A24 variant: the most recent worldwide pandemic was caused by progenies of a virus prevalent around 1981.

Nucleotide substitutions in the viral-encoded proteinase 3C (3Cpro) region (549 nucleotides) of the RNA genome of a coxsackievirus A24 variant (CA24v), one of the agents causing acute hemorrhagic conjunctivitis (AHC), were studied using 32 isolates collected from the Eastern hemisphere in 1970-1989. Based on regression analysis of nucleotide differences among isolates, the nucleotide substitution rate of CA24v 3Cpro was estimated to be 3.7 x 10(-3)/nucleotide/year. A phylogenetic tree constructed by the modified unweighted pair group method using arithmetic averages (UPGMA) indicated that CA24v had evolved from a common ancestor which appeared in one focal place in November 1963 +/- 21 months, about 7 years before the first isolation of CA24v in Singapore. The tree also revealed that all the recent epidemic isolates in 1985-1989 including Asian and Ghanian strains diverged from each other after 1981. This finding is consistent with the evidence that AHC due to CA24v had been confined to Southeast Asia and the Indian subcontinent until 1985, then suddenly and explosively spread to other areas where no CA24v isolations had been reported.

[Study on rapid diagnosis of acute hemorrhagic conjunctivitis caused by Coxsackievirus A24 variant].

An pandemic of acute hemorrhagic conjunctivitis (AHC) caused by Coxsackievirus A 24 variant (CA 24v) occurred in China in 1988. Rapid diagnosis of AHC was investigated by immunofluorescence technique. The bacteria-free conjunctival swab samples were inoculated into HeLa cell monolayer. The Virus-specific antigens in infected cells were examined by indirect immunofluorescence test. Of 35 samples, 17 was identified as CA 24v. The results of isolation and typing could be obtained with in 5 days. Further, CA 24v antigen in infected conjunctival cells were examined by indirect immunofluorescence test. Of 48 smears of conjunctival cells, 39 was positive. Positive rate were 81.3%.

[Etiology of 1988 epidemic of acute hemorrhagic conjunctivitis in Beijing].

An epidemic of acute hemorrhagic conjunctivitis (AHC) occurred in Beijing during August-September in 1988. Conjunctival swabs were collected from 50 AHC patients at the Eye Clinic of the Peking Union Medical College Hospital. 25 strains of viruses were isolated with Hela cell cultures. All the viral isolates were identified as Coxsackievirus A 24 variant (CA 24 v) with antiserum from the Center for Disease Control, U. S. A. Paired serum samples from 30 AHC patients were examined for neutralizing against a representative strain of the viral isolates. 24 of them (80%) showed a fourfold or greater rise in neutralizing antibody titers. The results indicate that CA 24 v was the etiologic agent responsible for the 1988 epidemic of AHC. This is the first time an epidemic of AHC caused by CA 24 v is reported in the mainland of China.

[An etiological study of acute hemorrhagic conjunctivitis in Beijing area in 1984].

Acute hemorrhagic conjunctivitis (AHC) has been widespread in China since 1971. An etiological survey of the sporadic outbreak in Beijing was done in 1984. Conjunctival swabs and sera were collected at the Eye Clinic of Peking Union Medical College Hospital and 10 strains of virus were isolated from 46 cases by culture on the HeLa cell line. 8 strains were identified as Enterovirus 70 by homologous antiserum J 670/71 obtained from the California State Laboratory of Viral and Rickettsial Diseases. 2 other strains defied neutralization by this antiserum and were eventually identified as Adenovirus type 3 and type 7. 30 paired sera were examined for neutralization antibodies to EV 70 (J 670/71). Among these, 23 (77%) showed fourfold or higher rise in titer. Furthermore, neutralization antibodies to EV70 (J 670/71) and the EV70 isolated from 7 patients with AHC by paired sera also showed a fourfold or higher rise in antibody titer, indicating that EV70 was the etiologic agent responsible for the 1984 outbreak in Beijing.

[Angiogenesis induced by SP2/0 and HeLa tumor cells].

Cheek pouches of Syrian golden hamsters and transparent access chambers of BALB/C mice were implanted with SP2/0 and HeLa tumor cells separately. Observation was done by continual photo and video from D 1 through the D 10 after implantation. It was found by the development of angiogenesis and the density of microvessels that both kinds of tumor cells could induce angiogenesis. On D 2 after implantation, there appeared leakage and hemorrhage from the microvessels near the tumor cells. On D 3 and D 4, there was an increased density of new capillaries which formed a very fine, tortuous and basketlike vascular plexus of irregular diameter. Most of the new microvessels came from the venules on the edge of the implant mass and they grew toward the tumor cells to penetrate the tumor tissue on D 4 to D 5. On D 7, the density of new microvessels reached the maximum and they began to extend outside the tumor which was surrounded by dense new capillaries. Compound 36 has been proved an effective substance against some tumors in clinical applications in this country. Also proved by our experiments, a drug effective in inhibition of angiogenesis induced by SP2/0 tumor cells.