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Biomedical subjects

M A Nowak

Publications and source records attributed to M A Nowak.

128 records · Page 8Linked to original sources

Mathematical biology of HIV infections: antigenic variation and diversity threshold.

Infection with the human immunodeficiency virus (HIV) results in severe damage to the immune system and consequent disease (AIDS) after a long and variable incubation period (on average 8-10 years). Why the incubation period should be so long is a puzzle. We outline an explanation based on the dynamics of the interplay between the immune response and antigenic variation in the virus population. The essential idea is that AIDS results when the diversity of antigenic variants of HIV in an infected patient exceeds some threshold, beyond which the immune system can no longer cope. The paper develops a simple mathematical model for this process, based on experimental observations, and explores several ramifications.

Acquired Immunodeficiency Syndrome↗

The evolutionary dynamics of HIV-1 quasispecies and the development of immunodeficiency disease.

This paper presents a theory to explain the development of immunodeficiency disease after a long and variable incubation period of infection with HIV-1. Two assumptions are central to the theory: (1) mutation via reverse transcription during viral replication can generate viral strains resistant to neutralization by antibodies specific to earlier mutants in a particular host; (2) the virus can kill the CD4-positive lymphocytes that play a role in mounting an immunological attack directed at the virus. The theory is examined via the development of a mathematical model which reveals that an increasing number of antigenically distinct viral strains may overwhelm the immune system of the host. As the viral diversity increases beyond a certain level the immune system is unable to suppress the population growth of all the strains simultaneously. The intuitive explanation of this pattern of model behaviour lies in the assumption that each virus can kill CD4-positive lymphocytes that are specific to any of the viral strains, but each lymphocyte only directs immunological attack against a single viral strain.(ABSTRACT TRUNCATED AT 250 WORDS)

Acquired Immunodeficiency Syndrome↗