The retrovirus family Retroviridae (Table 1) constitutes a large group of viruses that primarily infect vertebrates. They are enveloped RNA viruses, and each virion contains two identical copies of single-stranded RNA. The viral nucleic acid strands are surrounded by the structural proteins that form the nucleocapsid and the matrix shell. On the outer surface of the nucleocapsid and matrix protein is the lipid envelope derived from the host cell membrane. Proteins that mediate adsorption and penetration into the host cell membrane are inserted into the viral envelop. Retroviruses are unique, because they have the enzyme reverse transcriptase. Reverse transcriptase allows the viral RNA genome to be replicated into DNA and then RNA rather than directly into RNA.
Table1. Retroviruses
Amino acid sequencing of the reverse transcriptase protein divides the retrovirus family into groups. The human immunodeficiency viruses types 1 and 2 (HIV-1 and HIV-2) are members of this family as are the human T cell lymphoma viruses types 1 and 2 (HTLV-1 and HTLV-2). HIV-1 (Figure 1) is the more aggressive virus and is responsible for the acquired immunodefi ciency syndrome (AIDS) pandemic. The virus was first isolated in 1983, and a year later was proven to be associated with early and late stages of AIDS. HIV-2 was dis covered in 1986 and is less pathogenic. AIDS is the end stage of a process in which the immune system and its ability to control infections and malignant proliferation is destroyed. The virus has an affinity for the CD4+ surface marker of T lymphocytes. As the number of CD4+ T lymphocytes decreases, the risk and severity of opportunistic infections increases. Some of the most common opportunistic infections associated with HIV infection include disseminated coccidioidomycosis, cryptococcosis, cryptosporidiosis, histoplasmosis, recur rent pneumonia, and pneumocystis pneumonia. Detection of the HIV antibody is the mainstay of clinical diagnosis. Repeatedly reactive antibody tests done with EIA should be confirmed using Western blot testing (Figure 2). Clinical management of infected individuals involves the use of highly active antiretroviral therapy (HAART) and depends on the measurement of CD4+ lymphocytes and the viral load. Molecular methods often are used to quantify the viral load. Diagnosis of HIV infection in babies born to HIV-positive mothers is problematic because of maternal IgG in the baby’s blood; therefore, PCR for identification of viral DNA or RNA is recommended. Genome sequencing is used to establish susceptibility to antiviral agents.
Fig1. Usual time course of immune response, viremia, and disease resulting from untreated human immunodeficiency virus type 1 (HIV-1) infection. (Redrawn from Murray PR, Kobayashi GS, Pfaller MA et al, editors: Medical microbiology, ed 2, St Louis, 1992, Mosby.)
Fig2. Western blot test detecting specific human immunodeficiency virus (HIV) antibody. Lane 1 is the high-positive control; lane 2 is the low-positive control; lane 3 is the negative control; lanes 4 through 8 are positive sera; lane 9 is an indeterminate serum. Numbers at left refer to approximate molecular weights of HIV anti gens. (Courtesy R.L. Hodinka, Children’s Hospital of Philadelphia.)
The risk of laboratory-acquired infections with these viruses is a critical consideration; the greatest caution must be exercised in handling any specimens capable of harboring a blood-borne agent. Infection occurs through contamination of the hand and mucous membranes of the eyes, nose, or mouth with infected blood or other body fluids. No evidence exists of airborne transmission. Proper personal protective equipment must always be worn, including a laboratory gown, good-quality gloves, and eye protection. Disposable, unbreakable plastic ware should always be used in the handling of blood or bodily fluids.
HTLV-1 is endemic in the Caribbean, Africa, South and Central America, Melanesia, and Japan. However, only a small percentage of people infected (fewer than 4%) develop symptoms and disease. Cell-to-cell contact and TAX-induced clonal expansion of infected cells are the major avenues for viral replication, making detection of the virus difficult. As a result, serologic detection has remained the gold standard for diagnosis. Molecular detection and the development of PCR assays are being investigated in research laboratories. The average time from infection to the development of adult T-cell leukemia is approximately 40 years.
