The objective of the proposed study is to identify panels of seroepidemiological markers that reflect the clinical status of the individuals infected with HTLV-III/LAV. Such panels are valuable for the understanding of virus-host interactons, for differential diagnosis, prognosis, and for monitoring the effectiveness of drugs, immunotherapy, or vaccines. To achieve this, we propose to conduct a cross-sectional survey and a prospective study on serological profiles of the HTLV-III/LAV seropositivies include patients with AIDS or AIDs-Related Complex (ARC) and asymptomatic homosexuals, and to study H TLV-III/LAV antigen markers. The cross-sectional survey is chosen for its potential in providing answers in a relatively short period of time. The techniques of radioimmunoprecipitation and SDS-polyacrylamide gel electrophoresis, and immunoblotting (Western blot), which are routinely performed in our laboratory, will be employed to address issues concerning HTLV-III/LAV specific antigen markers. Uni- and multi-variate analyses for categorical data will be performed to analyze our results. If necessary, variables such as anti-body to selective domains of a given antigen, virus neutralizing antibody, antibody titer, and antibody isotypes to given antigen markers will also be evaluated. A cohort of 220 AIDS and ARC patients and asymptomatic homosexuals will be followed in our prospective study to monitor changes in their serological profiles. Serological markers surveyed in the cross-sectional study will be examined. Uni- and multi-variate analyses with changing marker(s) as independent variables will be performed to determine if prognostic markers for clinical and/or viremic status can be identified. Substantial emphasis will also be placed on the identification and characterization of previously unknown HTLV-III/LAV antigen markers in order to maximize the number of non-redundant markers that can be included in the serological marker panels mentioned above, and to screen for those who are infected by HTLV-III/LAV but lacking detectable antibody to any of the currently known antigen markers. The coding origins of newly identified protein antigens and antigenic domains will be determined by techniques of protein chemistry including radiosequence analysis, which has been used by us to identify several viral antigens of HTLV-I, HTLV-II and HTLV-III/LAV in the past.

Project Start
1986-04-01
Project End
1988-06-30
Budget Start
1987-04-01
Budget End
1988-06-30
Support Year
2
Fiscal Year
1987
Total Cost
Indirect Cost
Name
Harvard University
Department
Type
Schools of Public Health
DUNS #
082359691
City
Boston
State
MA
Country
United States
Zip Code
02115
Essex, M; Kanki, P J; Marlink, R et al. (1990) Antigenic characterization of the human immunodeficiency viruses. J Am Acad Dermatol 22:1206-10
Chou, M J; Lee, T H; Hatzakis, A et al. (1988) Antibody responses in early human immunodeficiency virus type 1 infection in hemophiliacs. J Infect Dis 157:805-11
Matsuda, Z; Chou, M J; Matsuda, M et al. (1988) Human immunodeficiency virus type 1 has an additional coding sequence in the central region of the genome. Proc Natl Acad Sci U S A 85:6968-72