Layne SP, Spouge JL, Dembo M; International Conference on AIDS.

Int Conf AIDS. 1989 Jun 4-9; 5: 633 (abstract no. Th.C.P.100).

Los Alamos National Laboratory, University of California, Los Alamos, NM, USA

OBJECTIVE: We present a model of the kinetic processes in viral infectivity assays. We show how the model is used for designing and analyzing viral infectivity assays, and discuss how it applies to questions such as - How many infectious virions are in an inoculum? How virulent are the virions in an inoculum? How stable are the virions in an inoculum? How effective are various chemical agents against the virions? How effective are immunoglobulins from infected individuals in neutralizing the virions? METHODS: Our model simulates the three overall steps that have been suggested for HIV's infective process. First, HIV diffuses to a target cells surface. Second, gp120 on the virus' surface and CD4 on the target cells surface form a bimolecular complex. Third, interactions involving CD4, gp120 and gp41 promote fusion of HIV envelope with target cell membrane, resulting in entry of the viral core. CONCLUSION: We have used the model to calculate the gp120-sCD4 association constant (k(assoc)) directly from viral infectivity assays. We find k(assoc) approximately 3x10(-9) M(-1), in agreement with equilibrium dialysis methods. We also report the values for the other parameters defined below. RESULTS: The model quantifies four rate-constants from viral infectivity assays: k(l) = rate constant for successful infective contact (tropism) between virus and a CD4+ target cell, k(s) = rate constant for spontaneous disassociation (shedding) of gp120 from gp41, k(n) = rate constant for non specific killing (e.g., by enzymatic degradation, nonoxynol-9, etc.) of virions, and k(assoc) = association constant for a gp120 blocking agent (e.g., soluble CD4 protein) or anti-gp120 immunoglobulin. These rate-constants are derived by straightforward graphical techniques.

Publication Types:

• Meeting Abstracts

Keywords:

• AIDS Vaccines
• Antigens, CD4
• HIV Envelope Protein gp120
• Nonoxynol
• SK&F 106528
• Virion
• immunology
• pathogenicity

Other ID:

• 00335289

UI: 102179254

From Meeting Abstracts