HIV variability and its implications for pathogenesis.
Int Conf AIDS 1994 Aug 7-12; 10:5 (abstract no. PS23) Goudsmit J; Human Retrovirus Laboratory, Academic Medical Center, Amsterdam, The Netherlands.
The natural history of HIV infection is characterized by extreme variability in the length of the symptom-free period. The length of the period from acute infection till the diagnosis of AIDS is determined by host and/or virus factors. Two determinants of the virus-host interaction appear to play a major role in the pathogenesis and natural history of HIV. Firstly the biological phenotype of the virus and secondly the replication level of the virus. Almost all new HIV infections are initiated by viruses of the non-syncytium-inducing (NSI) phenotype. During the acute infection the number of NSI viruses produced is in the range of 10(7-8)/ml plasma or blood irrespective of the subsequent length of the symptom-free period. In the first few years of infection NSI progressors can be distinguished from non-progressors on the basis of stable and high numbers of virions relative to declining virus numbers in non-progressors. Syncytium-inducing (SI) viruses can be isolated from about half of the progressors and such SI progressors can be distinguished from non-progressors on the basis of CD4+ cell decline while the virus load does not differentiate SI progressors from non-progressors in the first years after seroconversion. Envelope antibody responses and variation in the HIV envelope appear to play an important role in these early pathogenic events. Enhancement of replication following acute HIV infection may cause persistently high virus loads in NSI progressors. NSI virus neutralizing antibodies may cause a decline in viral burden in non-progressors, in at least half of these cases reversed by envelope mutations determining concomitantly decreased neutralization sensitivity and the SI phenotype. The phenotypic changes result subsequently in high virus loads, rapid CD4 decline and disease progression (the SI progressors). Results, based on the variation in genetic indicators of biological phenotype, number of virus replication cycles and neutralization resistance in the course of infection are represented confirming these notions.
Keywords: AEGIS, HIV, Acquired Immunodeficiency Syndrome, HIV Infections, Viral Load, Virus Replication, HIV Core Protein p24, Disease Progression, Giant Cells, HIV Envelope Protein gp120, HIV Antibodies, Variation (Genetics), Phenotype, Antigens, CD4, virology, genetics, ICA10
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