Contributions to Contemporary Neurology: A Tribute to Joseph Michael Foley

York.

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Acquired Immunodeficiency Syndrome: Virus Mutations and Clinical Surprises

Richard T. Johnson

Publisher Summary

This chapter describes the mutations and clinical surprises of AIDS virus. It is recognized that neurological complications develop in the majority of patients who have AIDS. Indeed, 10% of these patients present initially with neurological complaints. A wide variety of CNS and peripheral nervous system diseases complicate HIV infections. The aseptic meningitis reported in healthy, seropositive persons, and patients with AIDS-related complex is usually a benign, self-limited illness of minor clinical importance but possible major significance in pathogenesis. On several occasions, aseptic meningitis has occurred at the time of seroconversion and the virus has been isolated from cerebrospinal fluid. Vacuolar myelopathy is found in approximately 20% of patients with AIDS. Clinically this correlates with the development of progressive paraparesis accompanied by ataxia, spasticity, and incontinence. Histopathologically, the vacuolar degeneration of myelin is found in the dorsal and lateral columns without inflammation. Ultrastructural studies have demonstrated retrovirus-like particles within multinucleated cells, probably of macrophage origin.

The rapid changes of modern society and the almost infinite genetic variability of viruses combine to promise a future changing scene of unpredictable events. We live in interesting times….

Viral Infections of the Nervous System¹

I wrote these closing sentences of a book during the summer of 1981, at the same time that the Centers for Disease Control in Atlanta were receiving reports of strange occurrences of Pneumocystis pneumonia and Kaposi sarcoma among previously healthy gay men in New York and California.²,³ At the time, my comments and the public health reports seemed unrelated, but the reports were the harbingers of the current epidemic of the acquired immunodeficiency syndrome (AIDS), a new viral infection that has become the most ominous of all viral infections of the nervous system.

My references to changing social mores and virus mutations were not evidence of foresight or even insight–only a simple statement of facts. Greater sexual license had already facilitated the spread of genital herpes simplex virus. Genetic diversity of many viruses is found from isolate to isolate, and the evolution of new agents of varied virulence is an ongoing, dynamic process. New strains of influenza arise every decade;⁴ the neurovirulent La Crosse virus of the California serogroup appeared inexplicably in the Midwest in the 1960s;⁵ epidemic hemorrhagic conjunctivitis due to a new enterovirus (type 70) broke out abruptly in 1969 in Ghana and was originally called the Apollo disease because the first outbreak coincided with our first lunar landing.⁶

In a virus-infected cell, the burst of progeny from a single infectious particle allows many mutations in a single growth cycle. Rapid evolution is more dramatic among ribonucleic acid (RNA) viruses where the absence of proofreading endonucleases leads to a low fidelity of genome replication. The errors of incorporated nucleotides are estimated to be 10,000 to 100 million times greater in RNA than in deoxyribonucleic acid (DNA) replication, where proofreading occurs.⁷ In acute infections, wild-type virus usually outgrows the myriad of mutants, but variants with new disease-producing properties do rise within a species, and periodically a variant virus crosses normal species barriers. In viruses such as the retroviruses, where DNA pro virus is transcribed and incorporated into the host cell, these mutants accumulate. The evolution of new viruses in persistent infections is to be expected, but the magnitude of the problem with the new AIDS virus was certainly not