This report concerns the structure and function of human herpesviruses 6 and 7, their interactions with HIV, and interactions with T cells. We have recently shown that virus strains previously recognized as HHV- 6, isolated in the USA, Europe, and Japan, fall into two distinct categories. These virus groups have been tentatively designated as Exanthem Subitum Virus (or HHV-6) and HHV-8. HHV-7 was isolated in our laboratory in 1989, from CD4+ T cells of a healthy individual. Our studies this past year concerned several topics: (i) we have continued the derivation of approaches to be used in studies of HHV-7. Further cloning and mapping of HHV-7 DNA has been pursued. Sequences of the junction between the direct terminal repeat and the unique sequences have been analyzed. PCR primers have been derived and tested for specificity. (ii) We have continued our studies relevant to virus-host cell interactions. Our previous studies included analyses of the effect of T cell activation on virus replication, activation of HHV-6 and HHV-7 from latency, the effect of virus infection on T cell function, and analyses of parameters which determine entry into latency. We have analyzed HHV-6 sensitivity to interferon. We have shown the conditions for activation of HHV-6 and HHV-7 from latency. Entry and reactivation from latency are of potential medical importance, in as much as viral reactivation occurs in organ transplant and bone marrow transplant patients undergoing immunosuppression. (iii) In a study currently in progress, in collaboration with Dr. D. DiLuca of University of Ferrara, we have investigated the prevalence of HHV-7 DNA in Hodgkin's and non-Hodgkin's lymphomas. (iv) In recent studies, in collaboration with Dr. Sever of Childrens' Hospital, we have investigated whether HHV-6 plays a role as a cofactor, in the rapid development of AIDS in children to HIV+ mothers. Preliminary results have been obtained and future prospective studies have been designed. (v) We are attempting to characterize the microenvironment of the CD4 molecule on T cells. Further studies are planned.

Agency
National Institute of Health (NIH)
Institute
National Institute of Allergy and Infectious Diseases (NIAID)
Type
Intramural Research (Z01)
Project #
1Z01AI000540-06
Application #
3768827
Study Section
Project Start
Project End
Budget Start
Budget End
Support Year
6
Fiscal Year
1993
Total Cost
Indirect Cost
City
State
Country
United States
Zip Code