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INTRODUCTION

Disease

Human immunodeficiency virus (HIV) is the cause of acquired immunodeficiency syndrome (AIDS).

Both HIV-1 and HIV-2 cause AIDS, but HIV-1 is found worldwide, whereas HIV-2 is found primarily in West Africa. This chapter refers to HIV-1 unless otherwise noted.

Important Properties

HIV is one of the two important human T-cell lymphotropic retroviruses (human T-cell leukemia virus is the other). HIV preferentially infects and kills helper (CD4) T lymphocytes, resulting in the loss of cell-mediated immunity and a high probability that the host will develop opportunistic infections. Other cells (e.g., macrophages and monocytes) that have CD4 proteins on their surfaces can be infected also.

HIV belongs to the lentivirus subgroup of retroviruses, which cause “slow” infections with long incubation periods (see Chapter 44). HIV has a cylinder-shaped (type D) core surrounded by an envelope containing virus-specific glycoproteins (gp120 and gp41) (Figures 45–1 and 45–2). The genome of HIV consists of two identical molecules of single-stranded, positive-polarity RNA and is said to be diploid. The HIV genome is the most complex of the known retroviruses (Figure 45–3). In addition to the three typical retroviral genes gag, pol, and env, which encode the structural proteins, the genome RNA has six regulatory genes (Table 45–1). Two of these regulatory genes, tat and rev, are required for replication, and the other four, nef, vif, vpr, and vpu, are not required for replication and are termed “accessory” genes.

FIGURE 45–1

Human immunodeficiency virus (HIV)—electron micrograph. Large arrow points to a mature virion of HIV that has just been released from the infected lymphocyte at the bottom of the figure. Small arrow (in bottom left of image) points to several nascent virions in the cytoplasm just prior to budding from the cell membrane. (Source: Dr. A. Harrison, Dr. P. Feirino, and Dr. E. Palmer, Public Health Image Library, Centers for Disease Control and Prevention.)

FIGURE 45–2

Cross-section of human immunodeficiency virus (HIV). In the interior, two molecules of viral RNA are shown associated with reverse transcriptase. Surrounding those structures is a rectangular nucleocapsid composed of p24 proteins. Note that the viral protease and integrase are also located within the nucleocapsid (in addition to the reverse transcriptase), but, for lack of space, are not shown in the figure. On the exterior are the two envelope proteins, gp120 and gp41, which are embedded in the lipid bilayer derived from the cell membrane. (Reproduced with permission from Green WC. Mechanisms of disease: the molecular biology of human immunodeficiency virus type I infection. NEJM. 1991;324[5]:309.)

FIGURE 45–3

The genome of human immunodeficiency virus (HIV). Above the line are the ...

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