Global epidemic of human T-cell lymphotropic virus type-I (HTLV-I)

Abstract

Infection with human T-cell lymphotrophic virus-I (HTLV-I) is now a global epidemic, affecting 10 million to 20 million people. This virus has been linked to life-threatening, incurable diseases: adult T-cell leukemia/lymphoma (ATLL) and HTLV-I-associated myelopathy/tropical spastic paraparesis (HAM/TSP). The cumulative lifetime risk of developing these incurable diseases is approximately 5% in asymptomatic patients. For the emergency physician practicing among patients from high-risk groups, HTLV-I and its associated diseases are presenting an increasing challenge. This report describes its transmission, seroprevalence, treatment, and methods of controlling spread of this retrovirus. Coinfection with HTLV-I and HIV has been shown to accelerate the progression of acquired immune deficiency syndrome (AIDS).

Introduction

Retroviruses were reported at the beginning of the century as filterable agents that produced transmissible tumors in chickens (1). A retrovirus isolated from mice with leukemia was identified in the 1950s as the first mammalian retrovirus. In 1964, Jarrett and associates isolated the feline leukemia retrovirus (FeLV) from cat lymphosarcoma cells (2). In 1973, Hardy and colleagues described seroepidemiologic data indicating that the FeLV was transmitted horizontally among cats in the normal domestic habitat (3). FeLV seropositivity was correlated with the development of lymphosarcomas in the animals. Despite these comprehensive investigations, the first human retrovirus, the human T-cell lymphotropic virus-I (HTLV-I), was not isolated until 1978. In 1970, Howard Temin and David Baltimore discovered the RNA-to-DNA transcription by retroviruses (4). This finding facilitated the isolation of mammalian retroviruses because the enzyme reverse transcriptase proved to be a sensitive footprint for these retroviruses. In 1976, Gallo and colleagues discovered a growth factor specific for mature T-lymphocytes, later designated as interleukin-2 (IL-2), which allowed T-lymphocytes to be maintained in continuous culture (5). Using these innovative technologies, Gallo and associates isolated a new retrovirus from cultured CD4+ T-lymphocytes of a patient with a cutaneous T-cell malignancy (6).

Retroviruses are enveloped viruses that have an electron-dense central core that surrounds two identical copies of the single-stranded viral RNA. Retroviruses have a unique replicative strategy. Retroviral (+)ssRNA (message sense single-stranded RNA) serves as a template for the virion RNA-dependent DNA polymerase (reverse transcriptase) and primer transfer RNAs. The RNA-dependent DNA polymerase uses (+)ssRNA to make an ssDNA copy. The ssDNA copy is initially hydrogen-bonded to its complementary (+)ssRNA. A virally encoded ribonuclease digests the ssRNA, and a complementary DNA strand is synthesized. The dsDNA is integrated into chromosomal DNA in the host cell nucleus.

The year 2000 marks the 20th anniversary of the discovery of the first human retrovirus: human T-cell lymphotropic virus-I (HTLV-I). Its discovery has had several notable implications. First, this retrovirus provided clear proof of a relationship between viruses and cancer. Second, the obvious association of HTLV-I with a neurologic disease similar to multiple sclerosis (MS) created an opportunity to study the mechanisms that lead to chronic demyelinating disease. Finally, its identification clearly facilitated the discovery and isolation of the human immunodeficiency virus (HIV), which has caused a global epidemic of a rapidly progressing fatal illness: acquired immune deficiency syndrome (AIDS). While the AIDS epidemic justifiably captured the attention of the most gifted scientists in the world, scientific attention to HTLV-I was drastically diminished, permitting the development of a global epidemic of HTLV-I that causes fatal, chronic diseases. For the emergency physician practicing among patients from high-risk groups, HTLV-I and its associated diseases are presenting an increasing challenge. Consequently, this report describes its transmission, seroprevalence, associated diseases, treatment, and methods of controlling infection.