How does HIV know to attack specific immune system cells?

I'm no biologist, but curious of the answer to which I could not find online.

How are Human Immunodeficiency viruses able to detect and distinguish immune system cells with a CD4 receptor on the surface from other cells in the body, in particular other immune system cells without the receptor?

If I have asked the question on the wrong platform, please inform me otherwise.


The CD4 receptor is a protein complex that harbors very specific chemistry. A virus is able to bind with the receptor if it harbors a particular protein/set of proteins that are able to interact with the receptor. The virus is basically disguised as something the CD4 receptor recognizes, and from there it is internalized within the cell via a process called endocytosis. You can google viral endocytosis to learn more.

Mast cell

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Mast cell, tissue cell of the immune system of vertebrate animals. Mast cells mediate inflammatory responses such as hypersensitivity and allergic reactions. They are scattered throughout the connective tissues of the body, especially beneath the surface of the skin, near blood vessels and lymphatic vessels, within nerves, throughout the respiratory system, and in the digestive and urinary tracts. Mast cells store a number of different chemical mediators—including histamine, interleukins, proteoglycans (e.g., heparin), and various enzymes—in coarse granules found throughout the cytoplasm of the cell. Upon stimulation by an allergen, the mast cells release the contents of their granules (a process called degranulation) into the surrounding tissues. The chemical mediators produce local responses characteristic of an allergic reaction, such as increased permeability of blood vessels (i.e., inflammation and swelling), contraction of smooth muscles (e.g., bronchial muscles), and increased mucus production.

German medical scientist Paul Ehrlich was the first to describe mast cells, doing so in his doctoral thesis (1878). That mast cells are involved in inflammation and allergic reactions was not realized until the mid-20th century, however, and since that time mast cells have been found to participate in other immune phenomena, including autoimmune disease and innate and adaptive immune responses.

This article was most recently revised and updated by Kara Rogers, Senior Editor.

Can you explain AIDS and how it affects the immune system? How does HIV become AIDS?

The acquired immune deficiency syndrome (AIDS) was first recognized in the early 1980s. AIDS is caused by the human immunodeficiency virus (HIV) and is spread through the exchange of body fluids (sexual encounters, sharing needles, blood transfusions). Recent research suggests the virus "jumped" to humans from a West African subspecies of chimpanzee (Pan troglodytes troglodytes) intermittently decades or even centuries ago. The World Health Organization (WHO) estimates that millions are infected with HIV worldwide and that it is the most devastating epidemic since the influenza pandemic of 1918. There are some predictions that HIV will not be controlled until the middle of the next century and that it may continue to devastate developing countries for the next 100 years.

HIV is a unique human RNA virus, capable of infecting cells of the immune system. Specifically, HIV targets T helper cells (CD4 cells), leading to the eventual death of the cell. CD4 cells are vital players in the regulation of immune responses to invading microorganisms. In an untreated person, 10 billion to 100 billion new viruses are produced per day. This massive viral replication leads to a progressive loss of CD4 cells over a period of several years to as long as a decade. And destruction of CD4 cells renders a patient vulnerable to unusual opportunistic infections (OIs) that are rarely seen in healthy humans. Most patients who die from AIDS succumb to one or more OIs.

AIDS denotes the later stages of the disease and is not diagnosed until the patient has developed a significant OI or the CD4 cell count in the bloodstream falls below 200 (normal is 500 to 1,000 cells per milliliter). Therefore, infection with HIV does not necessarily mean AIDS, but all patients with AIDS have HIV infection.

Until 1996, HIV infection was fatal in the vast majority of infected individuals. With recent advances in understanding the virus life cycle, how and where the virus damages the immune system, and the action of new drugs, however, the course of AIDS in many patients in the developed world has dramatically changed. In fact, patients are doing so well that the term AIDS may have outlived its usefulness.

Combinations of drugs such as nucleoside reverse transcriptase inhibitors and protease inhibitors can help control viral replication, restore immune function and maintain health. We have seen patients literally on their deathbed return to full-time employment. The bad news is that long-term toxicity to virtually all these drugs has increasingly been recognized as patients take these medications for longer periods of time. In addition, patients must take the combination (commonly called HAART, for highly active anti-retroviral therapy) exactly as prescribed. If adherence to the regimen is not perfect, HIV can quickly become resistant to the medication. And once an initial combination fails, it is less likely a second, different combination will be effective. The good news is that newer drugs active against resistant viral strains and newer approaches to treatment are on the way. It is also important to note that HIV research may lead to advances in the treatment of other viral infections, as well as cancers, metabolic diseases (diabetes, high cholesterol) and other immune system disorders.

The major needs for the future include an effective preventive vaccine, new drugs, better understanding of the long-term side effects of the current drugs and improved health care delivery to people in the developing world. Perhaps the most important short-term need is effective prevention strategies. AIDS is a preventable infection better prevention will significantly decrease the tremendous burden HIV infection places on humans around the globe.

7.7: Specific acquired immunity

Antigens trigger specific immune responses. Antigens are substances which can trigger specific immune responses. When the immune system is working correctly, antigens are any substance that is &ldquoforeign&rdquo or &ldquonon-self&rdquo, such as invading pathogens. (Sometimes the immune system malfunctions and ones own cells or cell components trigger an immune response. When this occurs, it is referred to as &ldquoautoimmune&rdquo disease.) A bacterium can trigger production of antibodies and thus the bacterium is called &ldquoantigenic&rdquo. Different parts of the bacterium will trigger production of different antibodies. Each of these different parts is called an &ldquoantigenic determinant&rdquo or &ldquoepitope&rdquo. In class however, we will use the general term &ldquoantigen&rdquo to describe the part of a microbe to which antibodies bind.

Humoral immunity and antibodies/immunoglobulins

In humans, there are 5 classes of antibodies (ab) also called immunoglobulins (Ig). The predominant class and most versatile antibodies are called &ldquoIgG&rdquo. They represent approximately 70-80% of the antibodies in a human and can be found in blood and other tissue fluids.

Structure of IgG

igG is made of 4 polypeptide or protein chains. These chains are organized to forma a roughly &ldquoy&rdquo shaped molecule. The tipes of the arms are called &ldquoantigen-binding sites&rdquo. The arm tips have grooves with a specific shape and size which permit the antibody to bind to complementary antigen. Once bound to the antigen, the antibodies carry out several beneficial functions.

Functions of Antibodies

  1. agglutination of cells: inhibit movement of pathogens, increase phagocytosis by neutrophils and macrophages (agglutination=&rdquoclumping&rdquo)
  2. neutralization: antibodies binding to pathogen adhesins block attachment of pathogens to host cell surface receptors thus block colonization and disease. Antibodies can also bind toxins, preventing the toxin from binding host cells (antibodies to toxins are called &ldquoantitoxins&rdquo)
  3. opsonization : recall opsonization (literally &ldquopreparing to eat&rdquo) is the process in which a pathogen is coated with a &ldquosticky&rdquo substance such as complement, making the coated pathogen easier for the phagocytic cells to attach to and kill the pathogen. Antibodies can also opsonize pathogens. When an antibody binds to the surface of a pathogen, the antibody &ldquotail&rdquo sticks outward (the antibody tail is called the Fc fragment). Phagocytic cells have surface receptors which can bind to the antibody tails, permitting them to attach easier to the pathogen, thus increasing pathogen killing.
  4. Complement activation: when antibodies bind antigens, the antibodies can trigger activation of the complement pathway. Recall activation of the complement pathway has several advantages including:
    • triggering inflammation (increase blood flow, increase delivery of phagocytic cells, chemical gradients to guide phagocytic cells to sites of invasion)
    • complement proteins also act as opsonins thus help increase phagocytic killing of pathogens
    • complement proteins help guide phagocytic cells to site of injury/invasion
    • complement proteins can form membrane attack complexes &ldquoMAC attack&rdquo to help kill invading microbes by lysis.

Classes of antibodies

As mentioned earlier, IgG is one of 5 antibody classes in humans. The other classes include:

  • IgM: a large pentamer (5 parts), the first antibody produced in specific immune reactions. So large it is difficult to leave blood vessels. Can activate complement, can cause agglutination but NOT opsonic
  • sIgA = secretory IgA a dimmer (2 parts): VERY important antibody in mucous secretions. Important role in binding pathogens or toxins on mucous membrane to inhibit attachment to host cells. Essential component of specific mucosal immunity
  • IgE : important in allergic/hypersensitivity reactions. Bind to mast cells, help trigger release of histamine when allergen is encountered.
  • IgD : surface receptor on B lymphocytes

Which cells make antibodies? B-lymphocytes/plasma cells

When humoral immunity is triggered, antibodies are produced by B lymphocytes. Lymphocytes are one type of white blood cell or leukocyte which functions in the immune system. B lymphocytes are so named because they were first identified in chickens (!). Lymphocytes originate in bone marrow then mature under guidance of special chemicals produced in different environments. Upon maturation they will carry out different functions. In chickens, lymphocytes which mature under the chemical influence of the &ldquoBursa of Fabricus&rdquo mature into &ldquoB&rdquo (Bursa) lymphocytes. Humans lack a Bursa of Fabricus. It is thought B lymphocytes may mature in the bone marrow of human or in lymphoid tissue associated with the intestine (GALT=gut associated lymphoid tissue)

B lymphocytes are programmed to produce antibodies when stimulated by the appropriate antigen (more later). Once the B lymphocytes are stimulated, they mature into antibody producing plasma cells.

Clonal Selection, Expansion and Memory Cells

How are we able to specifically respond to the antigens of an invading pathogens? The key is the surface receptors on our lymphocytes. We have an incredible variety of lymphocytes circulating in our blood stream and through our lymphatic system. Each lymphocyte carries a different surface receptor. Each surface receptor can bind to a different antigen. Once the surface receptor binds its specific antigen (selection), it helps trigger the lymphocyte to start dividing (clonal expansion) and to start maturing into a functional lymphocyte. When a lymphocyte starts dividing, it divides into two populations of cells: effector cells and memory cells.

  1. Effector cells: these lymphocytes start immediately &ldquoto work&rdquo, they carry out the specific function of the lymphocyte. For example B lymphocyte effectors are the B lymphocytes which actually start producing antibodies (they have the specific name &ldquoplasma cells&rdquo when they start making antibodies)
  2. Memory cells: these memory lymphocytes do not start to work immediately. Instead, their job is to &ldquolive long&rdquo and &ldquoremember&rdquo the antigen which first triggered the immune response, if it is ever encountered again. The memory cells increase the number of lymphocytes which could respond to the antigen if it is ever encountered again. The memory cells are also &ldquoprimed&rdquo to trigger a faster immune response the second time the antigen is encountered. The memory cells are what proved us with &ldquoimmunological memory&rdquo, the reason vaccines work and the reasons some people develop &ldquolife-long&rdquo immunity once they recover from some infectious diseases. When memory cells are subsequently triggered by exposure to the same antigen that triggered the first (primary) immune response, the memory cells trigger a &ldquosecondary&rdquo immune response.

The secondary immune response is faster, stronger and longer lasting than the primary immune response.

Are only B lymphocytes involved in antibody production?

Although it would make our lives easier as students if only B lymphocytes were involved in antibody production, the process is much more complicated. The BEST humoral immunity is triggered when antigens trigger activation of 3 types of leukocytes/WBC&rsquos. The 3 types of cells are called:

  1. Antigen-Presenting Cell or &ldquoAPC&rdquo a macrophage is a classic example of an APC
  2. T helper lymphocyte: The MOST IMPORTANT cell of our immune system. T helpers literally help all the other cell of the immune system to function properly. The T helpers have a surface molecule called &ldquoCD4&rdquo. For this reason, T helpers are also called &ldquoCD4+&rdquo cells or &ldquoCD4+&rdquo lymphocytes. Tragically, HIV targets and destroys our CD4+ T helper lymphocytes, thus crippling our immune system, causing AIDS. (note: T lymphocyte originate in the bone marrow then travel to the thymus gland where they mature into T (thymus) lymphocytes)
  3. B lymphocyte: the actual antibody producer

There 3 cells interact with specific antigen and produce chemical messengers which enable each to carry out specific functions. Although we will briefly go over the process in lecture, what is most important to remember is that B cells need T helper lymphocytes to produce memory cells and to &ldquoswitch&rdquo to IgG production.

Summary of how APC. T helper and B lymphocytes interact with antigen to trigger antibody production-YOU DO NOT NEED TO KNOW DETAILS:

How does HIV know to attack specific immune system cells? - Biology

Physical and Chemical Barriers (Innate Immunity)

  • The skin has thick layer of dead cells in the epidermis which provides a physical barrier. Periodic shedding of the epidermis removes microbes.
  • The mucous membranes produce mucus that trap microbes.
  • Hair within the nose filters air containing microbes, dust, pollutants
  • Cilia lines the upper respiratory tract traps and propels inhaled debris to throat
  • Urine flushes microbes out of the urethra
  • Defecation and vomiting -expel microorganisms.
  • Lysozyme, an enzyme produced in tears, perspiration, and saliva can break down cell walls and thus acts as an antibiotic (kills bacteria)
  • Gastric juice in the stomach destroys bacteria and most toxins because the gastric juice is highly acidic (pH 2-3)
  • Saliva dilutes the number of microorganisms and washes the teeth and mouth
  • Acidity on skin inhibit bacterial growth
  • Sebum (unsaturated fatty acids) provides a protective film on the skin and inhibits growth
  • Hyaluronic acid is a gelatinous substance that slows the spread of noxious agents

Nonspecific Resistance (Innate Immunity)

  • Phagocytic cells ingest and destroy all microbes that pass into body tissues. For example macrophages are cells derived from monocytes (a type of white blood cell). Macrophages leave the bloodstream and enter body tissues to patrol for pathogens. When the macrophage encounters a microbe, this is what happens:
    1. The microbe attaches to the phagocyte.
    2. The phagocyte's plasma membrane extends and surrounds the microbe and takes the microbe into the cell in a vesicle.
    3. The vesicle merges with a lysosome, which contains digestive enzymes.
    4. The digestive enzymes begin to break down the microbe. The phagocyte uses any nutrients it can and leaves the rest as indigestible material and antigenic fragments within the vesicle.
    5. The phagocyte makes protein markers, and they enter the vesicle.
    6. The indigestible material is removed by exocytosis.
    7. The antigenic fragments bind to the protein marker and are displayed on the plasma membrane surface. The macrophage then secretes interleukin-1 which activates the T cells to secrete interleukin 2, as described below under specific resistance .
  • Inflammation is a localized tissue response that occurs when your tissues are damaged and in response to other stimuli. Inflammation brings more white blood cells to the site where the microbes have invaded. The inflammatory response produces swelling, redness, heat, pain
  • Fever inhibits bacterial growth and increases the rate of tissue repair during an infection.

Specific Resistance (Acquired Immunity)

  1. When an antigen is detected by a macrophage (as describe above under phagocytosis), this causes the T-cells to become activated.

    The activation of T-cells by a specific antigen is called cell-mediated immunity. The body contains millions of different T-cells, each able to respond to one specific antigen.

  2. The T-cells secrete interleukin 2. Interleukin 2 causes the proliferation of certain cytotoxic T cells and B cells.
  3. From here, the immune response follows 2 paths: one path uses cytotoxic T cells and the other uses B cells.
  • The cytotoxic T cells are capable of recognizing antigens on the surface of infected body cells.
  • The cytotoxic T cells bind to the infected cells and secrete cytotoxins that induce apoptosis (cell suicide) in the infected cell and perforins that cause perforations in the infected cells.
  • Both of these mechanisms destroys the pathogen in the infected body cell.

Click here for an animation on cytotoxic T cells.

The animation is followed by practice questions. Click here for even more practice questions.

Activation of a helper T cell and its roles in immunity:

T Cell Pathway

  • T-cells can either directly destroy the microbes or use chemical secretions to destroy them.
  • At the same time, T cells stimulate B cells to divide, forming plasma cells that are able to produce antibodies and memory B cells.
  • If the same antigen enters the body later, the memory B cells divide to make more plasma cells and memory cells that can protect against future attacks by the same antigen.
  • When the T cells activate (stimulate) the B cells to divide into plasma cells, this is called antibody-mediated immunity.

Click here for an animation on the immune response.

The animation is followed by practice questions.

  • IgG
  • IgM
  • IgA
  • IgE
  • IgD

There are 3 major types of T cells:

These cells secrete interleukin 2 (I-2) which stimulates cell division of T cells and B cells. In other words, these cells recruit even more cells to help fight the pathogen.

These cells remain dormant after the initial exposure to an antigen. If the same antigen presents itself again, even if it is years later, the memory cells are stimulated to convert themselves into cytotoxic T cells and help fight the pathogen.

This material is based upon work supported by the Nursing, Allied Health and Other Health-related Educational Grant Program, a grant program funded with proceeds of the State&rsquos Tobacco Lawsuit Settlement and administered by the Texas Higher Education Coordinating Board.

33 Review Questions

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This text is based on Openstax Biology for AP Courses, Senior Contributing Authors Julianne Zedalis, The Bishop's School in La Jolla, CA, John Eggebrecht, Cornell University Contributing Authors Yael Avissar, Rhode Island College, Jung Choi, Georgia Institute of Technology, Jean DeSaix, University of North Carolina at Chapel Hill, Vladimir Jurukovski, Suffolk County Community College, Connie Rye, East Mississippi Community College, Robert Wise, University of Wisconsin, Oshkosh

This work is licensed under a Creative Commons Attribution-NonCommercial 4.0 Unported License, with no additional restrictions

An immune response is generally divided into innate and adaptive immunity. Innate immunity occurs immediately, when circulating innate cells recognize a problem. Adaptive immunity occurs later, as it relies on the coordination and expansion of specific adaptive immune cells. Immune memory follows the adaptive response, when mature adaptive cells, highly specific to the original pathogen, are retained for later use.

Granulocytes include basophils, eosinophils, and neutrophils. Basophils and eosinophils are important for host defense against parasites. They also are involved in allergic reactions. Neutrophils, the most numerous innate immune cell, patrol for problems by circulating in the bloodstream. They can phagocytose, or ingest, bacteria, degrading them inside special compartments called vesicles.

Immune Tolerance

Tolerance is the prevention of an immune response against a particular antigen. For instance, the immune system is generally tolerant of self-antigens, so it does not usually attack the body's own cells, tissues, and organs. However, when tolerance is lost, disorders like autoimmune disease or food allergy may occur. Tolerance is maintained in a number of ways:

Inhibitory NK cell receptor (purple and light blue) binds to MHC-I (blue and red), an interaction that prevents immune responses against self.

  • When adaptive immune cells mature, there are several checkpoints in place to eliminate autoreactive cells. If a B cell produces antibodies that strongly recognize host cells, or if a T cell strongly recognizes self-antigen, they are deleted.
  • Nevertheless, there are autoreactive immune cells present in healthy individuals. Autoreactive immune cells are kept in a non-reactive, or anergic, state. Even though they recognize the body's own cells, they do not have the ability to react and cannot cause host damage.
  • Regulatory immune cells circulate throughout the body to maintain tolerance. Besides limiting autoreactive cells, regulatory cells are important for turning an immune response off after the problem is resolved. They can act as drains, depleting areas of essential nutrients that surrounding immune cells need for activation or survival.
  • Some locations in the body are called immunologically privileged sites. These areas, like the eye and brain, do not typically elicit strong immune responses. Part of this is because of physical barriers, like the blood-brain barrier, that limit the degree to which immune cells may enter. These areas also may express higher levels of suppressive cytokines to prevent a robust immune response.

Fetomaternal tolerance is the prevention of a maternal immune response against a developing fetus. Major histocompatibility complex (MHC) proteins help the immune system distinguish between host and foreign cells. MHC also is called human leukocyte antigen (HLA). By expressing paternal MHC or HLA proteins and paternal antigens, a fetus can potentially trigger the mother's immune system. However, there are several barriers that may prevent this from occurring: The placenta reduces the exposure of the fetus to maternal immune cells, the proteins expressed on the outer layer of the placenta may limit immune recognition, and regulatory cells and suppressive signals may play a role.

Read more about MHC proteins in Communication.

Transplantation of a donor tissue or organ requires appropriate MHC or HLA matching to limit the risk of rejection. Because MHC or HLA matching is rarely complete, transplant recipients must continuously take immunosuppressive drugs, which can cause complications like higher susceptibility to infection and some cancers. Researchers are developing more targeted ways to induce tolerance to transplanted tissues and organs while leaving protective immune responses intact.

Tandem changes

The biological function of PD-1 is not fully understood, but it is thought that it may be involved in preventing autoimmune reactions – where the white blood cells attack the body’s own cells.

Walker and his collaborators examined CD8 cells from 71 untreated HIV-positive patients in Durban, South Africa. They found that the more virus the patients had in their bodies, the more PD-1 they had on their CD8 cell surfaces.

But when Walker massively suppressed the amount of virus circulating in their blood by giving the patients antiretroviral drugs, the amount of PD-1 on their CD8 cells went down too, suggesting that the two rise and fall in tandem.

The same phenomenon was demonstrated in 19 North American individuals by a team led by Rafick-Pierre Sekaly at the Central Hospital of Montreal in Canada.

How HIV Destroys Immune Cells

Dan Cossins
Dec 19, 2013

HIV-infected T cell FLICKR, NIAID HIV leads to AIDS primarily because the virus destroys essential immune cells called CD4 T cells, but precisely how these cells are killed has not been clear. Two papers published simultaneously today (December 19) in Nature and Science reveal the molecular mechanisms that cause the death of most CD4 T cells in lymphoid tissues, the main reservoir for such cells, during infection.

Two research teams led by Warner Greene at the Gladstone Institutes in San Francisco have demonstrated that the vast majority of CD4 T cells in lymphoid tissues, despite their ability to resist full infection by HIV, respond to the presence of viral DNA by sacrificing themselves via pyroptosis&mdasha highly inflammatory form of cell death that lures more CD4 T cells to the area, thereby creating a vicious cycle that ultimately wreaks havoc on the immune system.

Richard Koup, who leads the immunology lab at the Vaccine Research Center at the NIH, agreed: “For years we’ve just said ‘HIV infects the cells and kills them,’ but it’s clearly more complicated than that. These papers start to delineate the multiple different mechanisms that HIV might have to kill CD4 T cells.”

“This cell-death pathway links the two signatures of HIV disease progression—that is, CD4 T cell-depletion and chronic inflammation—for the first time,” added Greene, who directs the Gladstone Institute of Virology and Immunology. What’s more, an existing anti-inflammatory drug can block the pathway, raising the prospect of new therapies that target the host response rather than the virus.

The death of CD4 T cells during HIV infection has generally been attributed to plain old apoptosis, or programmed cell death. Problem is, most studies have focused on active cells in the blood, which are “productively infected” by HIV, meaning that the virus has integrated with host-cell genome and can make copies of itself. In a 2010 study, Greene and his colleagues showed that 95 percent of CD4 T cells in lymphoid tissue, by contrast, are bystander cells that are “abortively infected”—the virus penetrates but can’t integrate or replicate. To better understand HIV pathogenesis, Greene sought to figure out how this particular population of immune cells dies during HIV infection.

For the study published in Nature, the team looked at human spleen and tonsil tissue cultured in the lab and spiked with HIV. The researchers found that when the virus productively infects the few permissive CD4 T cells present, death occurs through apoptosis mediated by an enzyme called caspase-3. But when HIV abortively infects nonpermissive CD4 T cells, death occurs by pyroptosis, which depends on the activation of caspase-1. It turns out that the vast majority—roughly 95 percent—of CD4 T cell death in lymphoid tissues is driven by caspase-1-mediated pyroptosis.

In bacterial infection, the release of inflammatory signals is thought to promote clearance by attracting more immune cells to help. In a pathogenic inflammation scenario like HIV infection, however, the strategy backfires. Instead of clearing the infection, proinflammatory signals released by pyroptosis attract more cells into the infected tissue to die and, in turn, produce more inflammation. “The cavalry come riding in and fall victim to this same form of fiery cell death, turning their rifles on themselves,” says Greene.

In the Science study, Greene and colleagues used a technique called DNA affinity chromatography to identify proteins in the CD4 T cells that detect fragments of HIV DNA and alert the enzyme caspase-1. They identified six candidates that all bind HIV DNA, including one called IFI16, which is known to be part of the protein complex that initiates inflammatory immune responses. And when they genetically manipulated CD4 T cells to knock out IFI16, the researchers were able to inhibit pyroptosis.

The discoveries could help researchers come up with new treatments that restrain the hosts’ destructive response to HIV rather than the virus itself. The authors showed in the Nature study that an existing caspase-1 inhibitor—a drug already shown to be safe in humans—suppressed CD4 T-cell death and inflammation in cell culture. They are now planning a Phase II clinical trial to test its capacity to block pyroptosis in HIV-infected patients.

Fauci said such an approach would not replace antiretrovirals (ARVs), which suppress HIV replication and halt disease progression. But it could be used in combination in people who are dealing with highly resistant HIV strains to reduce the destruction of CD4 T cells and inflammation. “One of the things about blocking the host response is that it's very difficult for the virus to mutate to counteract it,” added Fauci.

Greene pointed out that a caspase-1 inhibitor might also provide a bridge therapy for the millions of people without access to ARVs. He added that such drugs might even prevent expansion of the reservoir of latent virus that lies low in memory CD4 T cells, which has so far precluded a cure for HIV/AIDS.

The dysregulated action of cytokines during chronic inflammation might stimulate the homeostatic proliferation of memory CD4 T cells. “If we get rid of chronic inflammation, will we stop the homeostatic proliferation and degrade the latent reservoir?” asked Greene. “That’s something we can test. If it does, caspase-1 inhibitors might—and I emphasize might—become a component of a curative cocktail.”

G. Doitsh et al., “Cell death by pyroptosis drives CD4 T-cell depletion in HIV-1 infection,” Nature, doi:10.1038/nature12940, 2013.

K. M. Monroe et al., “IFI16 DNA sensor is required for death of lymphoid CD4 T cells abortively infected with HIV,” Science, doi:10.1126/science.1243640, 2013.