Acquired Immunodeficiency Syndrome
At the conclusion of this chapter, the reader should be able to:
• Describe the etiology and viral characteristics of human immunodeficiency virus (HIV-1).
• Explain the epidemiology, including modes of transmission, and prevention of HIV-1.
• Discuss the signs and symptoms of various stages and the classification of HIV infection.
• Describe the immunologic manifestations and cellular abnormalities of HIV-1 infection.
• Explain the serologic markers and diagnostic evaluation of HIV.
• Compare the features of fourth generations HIV testing to other generations of testing.
• Analyze a representative HIV-1 case study.
• Correctly answer case study related multiple choice questions.
• Be prepared to participate in a discussion of critical thinking questions.
• Describe the principles of the Rapid HIV antibody test, GS HIV Combo Antigen/Antibody EIA, and simulation of HIV-1 Detection.
Etiology
Viral Characteristics
Viral Structure
The HIV-1 virus (Fig. 25-1) is composed of a lipid membrane, structural proteins, and glycoproteins that protrude. The viral genome consists of three important structural components—pol, gag, and env. These gene components code for various products (Table 25-1). Long terminal redundancies (LTRs) border these three components. HIV-2 has a different envelope and slightly different core proteins.
Table 25-1
Component | Product |
pol | Produces DNA polymerase |
Produces endonuclease | |
gag | Codes for p24 and for proteins such as p17, p9, and p7 |
env | Codes for two glycoproteins, gp41 and gp120 |
Cells infected with HIV can be examined with an electron microscope. The virus may appear as buds of the cell membrane particles. The virion has a double-membrane envelope and an electron-dense laminar crescent or semicircular cores. An intermediate, less electron-dense layer lies between the envelope and core. In a mature, free extracellular virion, the core appears as a bar-shaped nucleoid structure in cross section. This structure appears circular and is frequently located eccentrically. It is composed of structural proteins and glycoproteins that occupy the core and envelope regions of the particle. The virion consists of knoblike structures composed of a protein called glycoprotein (gp) 120, which is anchored to another protein called gp41. Each knob includes three sets of these protein molecules. The core of the virus includes a major structural protein called p25 or p24 encoded for by the gag gene. After human exposure, these and other viral components may induce an antibody response important in serodiagnosis (Table 25-2).
Table 25-2
HIV Proteins of Serodiagnostic Importance
Virus | Protein | Location | Gene |
HIV-1 | gp41 | Envelope (transmembrane protein) | env |
gp160/120 | Envelope (external protein) | env | |
p24 | Core (major structural protein) | gag | |
HIV-2 | gp34 | Envelope (transmembrane protein) | env |
gp140 | Envelope (external protein) | env | |
p26 | Core (major structural protein) | gag |
The env gene encodes for a polyprotein that contains numerous glycosylation sites. The glycoprotein gp160 is found on infected cells but is deficient on viral particles; however, gp160 gives rise to two glycoproteins, gp120 and gp41, which are associated with the viral envelope. The encoding genes and gene products, or antigens, of the AIDS virus may induce an antibody response after human exposure (Table 25-3).
Table 25-3
Encoding Genes and Antigens of AIDS Virus
Encoding Gene | Antigen |
gag | p55 |
gag | p24 |
gag | p17 |
pol | p66 |
pol | p51 |
sor | p24 |
env | gp160 |
env | gp120 |
env | gp41 |
3′ orf | p27 |
Viral Replication
The replication of HIV is complicated and involves several steps (Fig. 25-2). The HIV life cycle is that of a retrovirus (Box 25-1). Retroviruses are so named because they reverse the normal flow of genetic information. In body cells, the genetic material is DNA. When genes are expressed, DNA is first transcribed into messenger RNA (mRNA), which then serves as the template for the production of proteins. The genes of a retrovirus are encoded in RNA; before they can be expressed, the RNA must be converted into DNA. Only then are the viral genes transcribed and translated into proteins in the usual sequence.
Target Cells
The infectious process begins when the gp120 protein on the viral envelope binds to the protein receptor, called CD4, located on the surface of a target cell. HIV-1 has a marked preference for the CD4+ subset of T lymphocytes (Fig. 25-3). In addition to T lymphocytes, macrophages, peripheral blood monocytes, and cells in the lymph nodes, skin, and other organs also express measurable amounts of CD4 and can be infected by HIV-1. About 5% of the B lymphocytes may express CD4 and may be susceptible to HIV-1 infection. Macrophages may play an important role in spreading HIV infection in the body, both to other cells and to the target organs of HIV. Monocyte-macrophages enable HIV-1 to enter the immune-protected domain of the central nervous system (CNS), including the brain and spinal cord.
Replication
Retroviruses carry a single, positive-stranded RNA and use reverse transcriptase to convert viral RNA into DNA. The life cycle of the HIV-1 virus consists of five phases (see Box 25-1):
1. The virus attaches and penetrates target cells (e.g., lymphocytes) that express the CD4 receptor. After penetration, the virus loses its protein coat, exposing the RNA core.
2. Reverse transcriptase converts viral RNA into proviral DNA.
3. The proviral DNA is integrated into the genome (genetic complement of the host cell).
4. New virus particles are produced as a result of normal cellular activities of transcription and translation.
Epidemiology
Classification System
The revised definition of HIV infection, which applies to both HIV-1 and HIV-2, incorporates the reporting criteria for HIV infection and AIDS into a single case definition (Box 25-2). The revised HIV criteria apply to AIDS-defining conditions for adults and children that require laboratory evidence of HIV.
Infectious Patterns
HIV-1
The progression of the natural history and immunopathogenesis of HIV-1 infection can be demonstrated in six discrete stages (Fig. 25-4). These stages are based on the sequential appearance in plasma of HIV-1 viral RNA, the gag p24 protein antigen, antibodies that bind to fixed viral proteins. No matter how HIV-1 was acquired, the timing of the appearance of viral and other markers of infection is generally uniform and follows an orderly pattern.