HIV is a retrovirus that infects cells of the immune system, mainly CD4+ T lymphocytes, and causes progressive destruction of these cells. An infectious HIV particle consists of two RNA strands within a protein core, sur rounded by a lipid envelope derived from infected host cells but containing viral proteins (Fig. 1). The viral RNA encodes structural proteins, various enzymes, and proteins that regulate transcription of viral genes and the viral life cycle.

Fig1. Structure and genes of the human immunodeficiency virus (HIV). A, An HIV-1 virion is shown next to a T cell surface. HIV-1 consists of two identical strands of RNA (the viral genome) and associated enzymes, including reverse transcriptase, integrase, and protease, packaged in a cone-shaped core composed of the p24 capsid protein with a surrounding p17 protein matrix, all surrounded by a phospholipid membrane envelope derived from the host cell. Virally encoded envelope proteins (gp41 and gp120) bind to CD4 and chemokine receptors on the host cell surface. B, The HIV-1 genome consists of genes whose positions are indicated here as different-colored blocks. Some genes contain sequences that overlap with sequences of other genes, as shown by overlapping blocks, but are read differently by host cell RNA polymerase. Similarly shaded blocks separated by lines (tat, rev) indicate genes whose coding sequences are separated in the genome and require RNA splicing to produce functional messenger RNA. The major functions of the proteins encoded by different viral genes are listed. MHC, Major histocompatibility complex. (A, Modified from front cover, The new face of AIDS. Science 272:1841–2102, 1996. Copyright Terese Winslow. B, Modified from Greene WC: AIDS and the immune system. Copyright 1993 by Scientific American, Inc. All rights reserved.)

The life cycle of HIV consists of the following sequential steps: infection of cells, production of a DNA copy of viral RNA and its integration into the host genome, expression of viral genes, and production of viral particles (Fig. 2). HIV infects cells by virtue of its major envelope glycoprotein, called gp120 (for 120-kD glycoprotein), which binds to CD4 and to particular chemokine receptors on human cells (mainly CXCR4 and CCR5). The major cell types that express these surface molecules and thus may be infected by HIV are CD4+ T lymphocytes; additionally, macrophages and dendritic cells may acquire the virus mainly by phagocytosis. After binding to cellular receptors, the viral mem brane fuses with the host cell membrane, and the virus enters the cell’s cytoplasm. Here the virus is uncoated by viral protease, and its RNA is released. A DNA copy of the viral RNA is synthesized by the viral reverse transcriptase enzyme (a process characteristic of all retroviruses), and the DNA integrates into the host cell’s DNA by the action of the integrase enzyme. The integrated viral DNA is called a provirus. If the infected T cell is activated by some extrinsic stimulus, such as another infectious microbe or cytokines, the cell responds by turning on the transcription of many of its own genes and often by producing cytokines itself. A negative consequence of this normal protective response is that the cytokines, and the process of cellular activation, may activate the provirus, leading to production of viral RNAs and then proteins. The virus is then able to form a core structure, which migrates to the cell membrane, acquires a lipid envelope from the host, and is shed as an infectious viral particle, ready to infect another cell. The integrated HIV DNA provirus may remain latent within infected cells for months or years, hidden from the patient’s immune system (and even from antiviral therapies). It is believed that macrophages and follicular helper T cells are important reservoirs for the virus.

Fig2. Life cycle of human immunodeficiency virus (HIV). The sequential steps in HIV reproduction are shown, from initial infection of a host cell to release of new virus particles (virions).

Most cases of AIDS are caused by HIV-1 (i.e., HIV type 1). A related virus, HIV-2, causes some cases of the disease. 

مواضيع ذات صلة

Viral Pathogenesis

VIRUSES

Human Cytomegalovirus

Influenza Virus Infections in Humans

Varicella-Zoster Virus

Adenovirus Coinfection with SARS-CoV-2

Genetic Polymorphisms susceptibility to SARS-CoV-2

Acute viral hepatitis

Human receptor of coronavirus and Adenovirus

Antiviral Chemotherapy

Humoral Immune Responses to SARS-CoV-2 Infection

Cellular Immune Responses to SARS-CoV-2