WORLD OF MICROBIOLOGY AND IMMUNOLOGY Agar and agarose continuous over a longer time.Secondly.an adjuvant itself can together.When these bonds are severed.energy is released.In Thirdly.an adjuvant can als en down via a serie hag This ents more anti Hans Krbs).Aprinciple product of the Kreb's cycle D reactions of which oxygen is a key. acceptor in the process.Anaerobic tors is nitrate.and service e type ownasdenitrication ria called mycohacteria into a mix own process yield 38 molecules throughout the suspension.the mycobacteria and the immuno or that does ono ygen also generates ATP.bu Seeal Immunity:active,passive,and delayed The aerobic mode of energy productioncan AEROBES e structure in hich t react chondrion are c Bacteria,yeasts.fungi,and algac are capable of acrobic gro The opnosite of an aerobe is an anaerobe.An anaerobe Carbon cycle in microorganisms;Metabolism does not require oxygen,or sometimes cannot even tolerate ne p AGAMMAGLOBULINAEMIA WITH HYPER There are various degrecth of yen olerance ve IGM.see IMMUNODEFICIENCY DISEASE SYNDROMES so as to grow oxygen. AGAR AND AGAROSE a g the breakdown of yield energy.The energy is used to sis th energy insi tion.As the solution cools.the agar or aga e becomes gel heir constituent molecule like,rendering the medium in a semi-solid.When bacteria
WORLD OF MICROBIOLOGY AND IMMUNOLOGY Agar and agarose 5 • • continuous over a longer time. Secondly, an adjuvant itself can react with some of the cells of the immune system. This interaction may stimulate the immune cells to heightened activity. Thirdly, an adjuvant can also enhance the recognition and ingestion of the antigen by the immune cell known as the phagocyte. This enhanced phagocytosis presents more antigens to the other cells that form the antibody. There are several different types of antigens. The adjuvant selected typically depends on the animal being used to generate the antibodies. Different adjuvants produce different responses in different animals. Some adjuvants are inappropriate for certain animals, due to the inflammation, tissue damage, and pain that are caused to the animal. Other factors that influence the choice of an adjuvant include the injection site, the manner of antigen preparation, and amount of antigen injected. One type of adjuvant that has been of long-standing service in generating antibodies for the study of bacteria is known as Freund’s Complete Adjuvant. This type of adjuvant enhances the response to the immunogen of choice via the inclusion of a type of bacteria called mycobacteria into a mixture of oil and water. Typically, there is more oil present than water. The oil and water acts to emulsify, or spread evenly throughout the suspension, the mycobacteria and the immunogen. Sometimes the mycobacteria are left out of the adjuvant. In this case, it is referred to as “incomplete” adjuvant. See also Immunity: active, passive, and delayed AAerobes EROBES Aerobic microorganisms require the presence of oxygen for growth. Molecular oxygen functions in the respiratory pathway of the microbes to produce the energy necessary for life. Bacteria, yeasts, fungi, and algae are capable of aerobic growth. The opposite of an aerobe is an anaerobe. An anaerobe does not require oxygen, or sometimes cannot even tolerate the presence of oxygen. There are various degrees of oxygen tolerance among aerobic microorganisms. Those that absolutely require oxygen are known as obligate aerobes. Facultative aerobes prefer the presence of oxygen but can adjust their metabolic machinery so as to grow in the absence of oxygen. Microaerophilic organisms are capable of oxygen-dependent growth but cannot grow if the oxygen concentration is that of an air atmosphere (about 21% oxygen). The oxygen content must be lower. Oxygen functions to accept an electron from a substance that yields an electron, typically a substance that contains carbon. Compounds called flavoproteins and cytochromes are key to this electron transport process. They act as electron carriers. By accepting an electron, oxygen enables a process known as catabolism to occur. Catabolism is the breakdown of complex structures to yield energy. The energy is used to sustain the microorganism. A common food source for microorganisms is the sugar glucose. Compounds such as glucose store energy inside themselves, in order to bond their constituent molecules together. When these bonds are severed, energy is released. In aerobic bacteria and other organisms, a compound called pyruvic acid retains most of the energy that is present in the glucose. The pyruvic acid in turn is broken down via a series of reactions that collectively are called the tricarboxylic acid cycle, or the Kreb’s cycle (named after one the cycle’s discoverers, Sir Hans Krebs). A principle product of the Kreb’s cycle is a compound called nicotinamide adenine dinucleotide (NADH2). The NADH2 molecules feed into another chain of reactions of which oxygen is a key. The energy-generating process in which oxygen functions is termed aerobic respiration. Oxygen is the final electron acceptor in the process. Anaerobic respiration exists, and involves the use of an electron acceptor other than oxygen. One of the most common of these alternate acceptors is nitrate, and the process involving it is known as denitrification. Aerobic respiration allows a substrate to be broken down (this is also known as oxidation) to carbon dioxide and water. The complete breakdown process yields 38 molecules of adenine triphosphate (ATP) for each molecule of the sugar glucose. ATP is essentially the gasoline of the cell. Electron transport that does not involve oxygen also generates ATP, but not in the same quantity as with aerobic respiration. Thus, a facultative aerobe will preferentially use oxygen as the electron acceptor. The other so-called fermentative type of energy generation is a fall-back mechanism to permit the organism’s survival in an oxygen-depleted environment. The aerobic mode of energy production can occur in the disperse cytoplasm of bacteria and in the compartmentalized regions of yeast, fungi and algae cells. In the latter microorganisms, the structure in which the reactions take place is called the mitochondrion. The activities of the mitochondrion are coordinated with other energy-requiring processes in the cell. See also Carbon cycle in microorganisms; Metabolism AGAMMAGLOBULINAEMIA WITH HYPER IGM • see IMMUNODEFICIENCY DISEASE SYNDROMES AAgar and agarose GAR AND AGAROSE Agar and agarose are two forms of solid growth media that are used for the culture of microorganisms, particularly bacteria. Both agar and agarose act to solidify the nutrients that would otherwise remain in solution. Both agar and agarose are able to liquefy when heated sufficiently, and both return to a gel state upon cooling. Solid media is prepared by heating up the agar and nutrient components so that a solution results. The solution is then sterilized, typically in steam-heat apparatus known as an autoclave. The sterile medium is then poured into one half of sterile Petri plates and the lid is placed over the still hot solution. As the solution cools, the agar or agarose becomes gellike, rendering the medium in a semi-solid. When bacteria womi_A 5/6/03 1:06 PM Page 5
Agar and agarose WORLD OF MICROBIOLOGY AND IMMUNOLOGY contact the surface of the medium.they are able to extract the for the firs total and partial destruction of the constituent red blood cells Soon thereafter a flourishing agar manufacturing industry wa can be detected by their characteristic hemolytic reactions. called gelactos.This compound is in fact made up of e nde lled agarose Gelactose p nited S tates.the copious s was nam ned for the an Diego area a hotbed of agar manufac extracted from sale of agar be a source of agar gar as a means for growing microorganisms.Since this dis hat two a0可a overy.the use of agar The so tightly that water can be trapped inside the helix.Asmore of ased growth media.Some
Agar and agarose WORLD OF MICROBIOLOGY AND IMMUNOLOGY 6 • • contact the surface of the medium, they are able to extract the nutrients from the medium and grow as colonies. The use of agar and agarose solid media allows for the isolation of bacteria by a streak plate technique. A similar discrimination of one bacterial species from another is not possible in liquid growth media. Furthermore, some solid growth media allows reactions to develop that cannot develop in liquid media. The best-known example is blood agar, where the total and partial destruction of the constituent red blood cells can be detected by their characteristic hemolytic reactions. Agar is an uncharged network of strands of a compound called gelactose. This compound is in fact made up of two polysaccharides called agarose and agaropectin. Gelactose is extracted from a type of seaweed known as Gelidium comeum. The seaweed was named for the French botanist who first noted the gelatinous material that could be extracted from the kelp. Another seaweed called Gracilaria verrucosa can also be a source of agar. Agarose is obtained by purification of the agar. The agarose component of agar is composed of repeating molecules of galactopyranose. The side groups that protrude from the galactopyranose are arranged such that two adjacent chains can associate to form a helix. The chains wrap together so tightly that water can be trapped inside the helix. As more and more helices are formed and become cross-linked, a threedimensional network of water-containing helices is created. The entire structure has no net charge. The history of agar and agarose extends back centuries and the utility of the compounds closely follow the emergence and development of the discipline of microbiology. The gellike properties of agar are purported to have been first observed by a Chinese Emperor in the mid-sixteenth century. Soon thereafter, a flourishing agar manufacturing industry was established in Japan. The Japanese dominance of the trade in agar only ended with World War II. Following World War II, the manufacture of agar spread to other countries around the globe. For example, in the United States, the copious seaweed beds found along the Southern California coast has made the San Diego area a hotbed of agar manufacture. Today, the manufacture and sale of agar is lucrative and has spawned a competitive industry. The roots of agar as an adjunct to microbiological studies dates back to the late nineteenth century. In 1882, the renowned microbiologist Robert Koch reported on the use of agar as a means for growing microorganisms. Since this discovery, the use of agar has become one of the bedrock techniques in microbiology. There are now hundreds of different formulations of agar-based growth media. Some are nonspeAerobic fungus growing on agar. womi_A 5/6/03 1:06 PM Page 6
WORLD OF MICROBIOLOGY AND IMMUNOLOGY AIDS cific.with a spectrum of components present.Other media are clectrophoretic techniques.By manipulation of the formula tion co s,the aga ands,whic Thus the aga the basi d nature or agal t of samples such as pieces o cleic acid a n the no whins.and dessert gelatins hemolytic reaction on blood aga See also Bacterial growth and division:Laboratory techniques in microbiology quently diffuse out of the disk into the agar.This version of agar AGAR DIFFUSION for th resistance.More detailed analysis to ascertain the nature of the med by the gelling of agar.When pe resistance can then follow. he degree of the mo SeeAntibiotic resistance.tests for Laboratory techniques molecule This phenomenon forms the basis of the agar diffu 0g sion assay that including antiblotics. AGGLUTINATION.see ANTIBODY-ANTIGEN.BIOCHEM ICAL AND MOLECULAR REACTIONS polyme nall molecules such as AIDS is applied toawell that is cut The advent of AIDS(acquired immunity deficiency syndrome) ill tend to move from this n carly that time eliminating infectious dise AIDS.an infectious diseas syndrome that suppresse s the e system,Is ca devised in 1944. nsion is known as retr ruse The name AIDS was coined in face of the agar.Then,antibiotic is applied to a number of 1982. Followng the discovery of AIDS.scientists attempted resistant to t antibi If there is a clearing around the that cause on: an a Mor anc other was Americ t Gall ing disks of ar showed the pathogen to be a retrovirus,meaning that its interest directly onto the agar surface.The antibiotic will subs genetic material is RNA instead of DNA.Following the discov
WORLD OF MICROBIOLOGY AND IMMUNOLOGY AIDS 7 • • cific, with a spectrum of components present. Other media are defined, with precise amounts of a few set materials included. Likewise the use of agarose has proved tremendously useful in electrophoretic techniques. By manipulation of the formulation conditions, the agarose matrix can have pores, or tunnels through the agarose strands, which can be of different size. Thus the agarose can act as a sieve, to separate molecules on the basis of the size. The uncharged nature of agarose allows a current to be passed through it, which can drive the movement of samples such as pieces of deoxyribonucleic acid (DNA) from one end of an agarose slab to the other. The speed of the molecule movement, is also related to molecular size (largest molecules moving the least). In the non-microbiological world, agar and agarose have also found a use as stabilizers in ice cream, instant cream whips, and dessert gelatins. See also Bacterial growth and division; Laboratory techniques in microbiology AAgar diffusionGAR DIFFUSION Agar diffusion refers to the movement of molecules through the matrix that is formed by the gelling of agar. When performed under controlled conditions, the degree of the molecule’s movement can be related to the concentration of the molecule. This phenomenon forms the basis of the agar diffusion assay that is used to determine the susceptibility or resistance of a bacterial strain to an antibacterial agent, (e.g., including antibiotics. When the seaweed extract known as agar is allowed to harden, the resulting material is not impermeable. Rather, there are spaces present between the myriad of strands of agar that comprise the hardened polymer. Small molecules such as antibiotics are able to diffuse through the agar. Typically, an antibiotic is applied to a well that is cut into the agar. Thus, the antibiotic will tend to move from this region of high concentration to the surrounding regions of lower antibiotic concentration. If more material is present in the well, then the zone of diffusion can be larger. This diffusion was the basis of the agar diffusion assay devised in 1944. A bacterial suspension is spread onto the surface of the agar. Then, antibiotic is applied to a number of wells in the plate. There can be different concentrations of a single antibiotic or a number of different antibiotics present. Following a time to allow for growth of the bacteria then agar is examined. If bacterial growth is right up to the antibiotic containing well, then the bacterial strain is deemed to be resistant to the antibiotic. If there is a clearing around the antibiotic well, then the bacteria have been adversely affected by the antibiotic. The size of the inhibition zone can be measured and related to standards, in order to determine whether the bacterial strain is sensitive to the antibiotic. This technique can also be done by placing disks of an absorbent material that have been soaked with the antibiotic of interest directly onto the agar surface. The antibiotic will subsequently diffuse out of the disk into the agar. This version of agar diffusion is known as the Kirby-Bauer disk-diffusion assay. The agar diffusion assay allows bacteria to be screened in a routine, economical and easy way for the detection of resistance. More detailed analysis to ascertain the nature of the resistance can then follow. See also Antibiotic resistance, tests for; Laboratory techniques in microbiology AGGLUTINATION • see ANTIBODY-ANTIGEN, BIOCHEMICAL AND MOLECULAR REACTIONS AIDS AIDS The advent of AIDS (acquired immunity deficiency syndrome) in early 1981 surprised the scientific community, as many researchers at that time viewed the world to be on the brink of eliminating infectious disease. AIDS, an infectious disease syndrome that suppresses the immune system, is caused by the Human Immune Deficiency Virus (HIV), part of a group of viruses known as retroviruses. The name AIDS was coined in 1982. Victims of AIDS most often die from opportunistic infections that take hold of the body because the immune system is severely impaired. Following the discovery of AIDS, scientists attempted to identify the virus that causes the disease. In 1983 and 1984 two scientists and their teams reported isolating HIV, the virus that causes AIDS. One was French immunologist Luc Montagnier (1932– ), working at the Pasteur Institute in Paris, and the other was American immunologist Robert Gallo (1937– ) at the National Cancer Institute in Bethesda, Maryland. Both identified HIV as the cause of AIDS and showed the pathogen to be a retrovirus, meaning that its genetic material is RNA instead of DNA. Following the discovStaphylococcus colonies showing hemolytic reaction on blood agar. womi_A 5/6/03 1:06 PM Page 7
AIDS WORLD OF MICROBIOLOGY AND IMMUNOLOGY ery.a dispute ensued over who made the initial discovery.but sion is that a person who has had another sexually transmitted todayGalo.andMcontaenierrneitels6oniceomere called reverse transcriptas t assay (ELISA).(The e is another ed single s in dou 2.)First 1985 by R ynthesis of more viral RNA.The viral even though the disease attacks the immune system.Bcells Is and b oth a Tight the wi colorchan s and t 1)pat believeh ilityV-l originated in the region of nd 2)thos dition,ELIS suppress the mmune system second more spe Itest to con the pres ence o and sub duced by the virus and can therefo ale vith n,sep. AIDS.Unab dy HIV-2 mine the cause of death at the time. c o After HIV invades the body the dis e n s through During th fu-like as the cause of death in many AIDS s such as fever and headache within one thre des ho er,the whil their then relativ to miologists. ntists who the incidence. antibodies This stage co tinues for th AIL or Dis an effo ntibodie called CD4- attack States thr gh the hom es the cells tha ass the a populatio helpe ymphocyte t of HIV xuals with counti for eral month eral the disease es to th enty percent AID: and infe A new in ands may The CDC ha established a definition fo nics not mm of e eloping countri Afri has the has set hetween the s of 25 and 44 in the Unites States re nucleosides that are building blocks of DNA The enzyme ran from an infected n is t nd oral to ger AZT high risk of con An tors are admini n child ble to in s.In hughbat-IcJimg. Although rare in such as the or to be used in combina nsfus of infected bl ting factors.Another consideration regarding HIV transmis or in combination with nucleosides.The combination of drugs
AIDS WORLD OF MICROBIOLOGY AND IMMUNOLOGY 8 • • ery, a dispute ensued over who made the initial discovery, but today Gallo and Montagnier are credited as co-discoverers. Inside its host cell, the HIV retrovirus uses an enzyme called reverse transcriptase to make a DNA copy of its genetic material. The single strand of DNA then replicates and, in double stranded form, integrates into the chromosome of the host cell where it directs synthesis of more viral RNA. The viral RNA in turn directs the synthesis protein capsids and both are assembled into HIV viruses. A large number of viruses emerge from the host cell before it dies. HIV destroys the immune system by invading lymphocytes and macrophages, replicating within them, killing them, and spreading to others. Scientists believe that HIV originated in the region of sub-Saharan Africa and subsequently spread to Europe and the United States by way of the Caribbean. Because viruses exist that suppress the immune system in monkeys, scientists hypothesize that these viruses mutated to HIV in the bodies of humans who ate the meat of monkeys, and subsequently caused AIDS. A fifteen-year-old male with skin lesions who died in 1969 is the first documented case of AIDS. Unable to determine the cause of death at the time, doctors froze some of his tissues, and upon recent examination, the tissue was found to be infected with HIV. During the 1960s, doctors often listed leukemia as the cause of death in many AIDS patients. After several decades however, the incidence of AIDS was sufficiently widespread to recognize it as a specific disease. Epidemiologists, scientists who study the incidence, cause, and distribution of diseases, turned their attention to AIDS. American scientist James Curran, working with the Centers for Disease Control and Prevention (CDC), sparked an effort to track the occurrence of HIV. First spread in the United States through the homosexual community by male-to-male contact, HIV rapidly expanded through all populations. Presently new HIV infections are increasing more rapidly among heterosexuals, with women accounting for approximately twenty percent of the AIDS cases. The worldwide AIDS epidemic is estimated to have killed more than 6.5 million people, and infected another 29 million. A new infection occurs about every fifteen seconds. HIV is not distributed equally throughout the world; most afflicted people live in developing countries. Africa has the largest number of cases, but the fastest rate of new infections is occurring in Southeast Asia and the Indian subcontinent. In the United States, though the disease was concentrated in large cities, it has spread to towns and rural areas. Once the leading cause of death among people between the ages of 25 and 44 in the Unites States, AIDS is now second to accidents. HIV is transmitted in bodily fluids. Its main means of transmission from an infected person is through sexual contact, specifically vaginal and anal intercourse, and oral to genital contact. Intravenous drug users who share needles are at high risk of contracting AIDS. An infected mother has a 15 to 25% chance of passing HIV to her unborn child before and during birth, and an increased risk of transmitting HIV through breast-feeding. Although rare in countries such as the United States where blood is screened for HIV, the virus can be transmitted by transfusions of infected blood or blood-clotting factors. Another consideration regarding HIV transmission is that a person who has had another sexually transmitted disease is more likely to contract AIDS. Laboratories use a test for HIV-1 that is called Enzymelinked immunosorbant assay (ELISA). (There is another type of HIV called HIV-2.) First developed in 1985 by Robert Gallo and his research team, the ELISA test is based on the fact that, even though the disease attacks the immune system, B cells begin to produce antibodies to fight the invasion within weeks or months of the infection. The test detects the presence of HIV-1 type antibodies and reacts with a color change. Weaknesses of the test include its inability to detect 1) patients who are infectious but have not yet produced HIV-1 antibodies, and 2) those who are infected with HIV-2. In addition, ELISA may give a false positive result to persons suffering from a disease other than AIDS. Patients that test positive with ELISA are given a second more specialized test to confirm the presence of AIDS. Developed in 1996, this test detects HIV antigens, proteins produced by the virus, and can therefore identify HIV before the patient’s body produces antibodies. In addition, separate tests for HIV-1 and HIV-2 have been developed. After HIV invades the body, the disease passes through different phases, culminating in AIDS. During the earliest phase the infected individual may experience general flu-like symptoms such as fever and headache within one to three weeks after exposure; then he or she remains relatively healthy while the virus replicates and the immune system produces antibodies. This stage continues for as long as the body’s immune response keeps HIV in check. Progression of the disease is monitored by the declining number of particular antibodies called CD4-T lymphocytes. HIV attacks these immune cells by attaching to their CD4 receptor site. The virus also attacks macrophages, the cells that pass the antigen to helper T lymphocytes. The progress of HIV can also be determined by the amount of HIV in the patient’s blood. After several months to several years, the disease progresses to the next stage in which the CD4-T cell count declines, and nonlife-threatening symptoms such as weakness or swollen lymph glands may appear. The CDC has established a definition for the diagnosis of AIDS in which the CD4 T-cell count is below 200 cells per cubic mm of blood, or an opportunistic disease has set in. Although progress has been made in the treatment of AIDS, a cure has yet to be found. In 1995 scientists developed a potent cocktail of drugs that help stop the progress of HIV. Among other substances, the cocktail combines zidovudine (AZT), didanosine (ddi), and a protease inhibitor. AZT and ddi are nucleosides that are building blocks of DNA. The enzyme, reverse transcriptase, mistakenly incorporates the drugs into the viral chain, thereby stopping DNA synthesis. Used alone, AZT works temporarily until HIV develops immunity to the nucleoside. Proteases are enzymes that are needed by HIV to reproduce, and when protease inhibitors are administered, HIV replicates are no longer able to infect cells. In 1995 the Federal Drug Administration approved saquinaviras, the first protease inhibitor to be used in combination with nucleoside drugs such as AZT; this was followed in 1996 by approval for the protease inhibitors ritonavir and indinavir to be used alone or in combination with nucleosides. The combination of drugs womi_A 5/6/03 1:06 PM Page 8
WORLD OF MICROBIOLOGY AND IMMUNOLOGY AIDS,recent advances in research and treatment per microliter of blood,the number of infective virus particles the of the tening illnes s that nomally would d by an Until 2001.th ge of new Tcell wever.th t the In addition t cration in th los.Ev en though the AIDS es e in order t vise the mo mall fsionsdul exual interc e or dire detemined.perhaps the loss can be prevented.This would been an better equp ght the i unprecedented emphasisn public Ther pror icd n established.Highly Active Anti-Retroviral H AIDS ng a rugs t individuals at risk of spreading or contracting the disease oms of AIDS.The drug mixture typically con nalog See also AIDS.r in re arch and treatme blocks ge Disease Contol(DC):Epide mics.viral:Human enzyme in the making of new virus (protease and reverse e tran virus (HIV) dly reduced the loss of life due to ams nigues:Infection and resis But this benefit has come at the expe ase of side effects that can often be Also treatm But nov uses and dis nitted disea es;I cells o of Haart in a 7-dav-on 7-day ofr"cycle does not diminish does diminish treat infection ment side ther ac ment in aIDs treatn nt ma AIDS.RECENT ADVANCES IN RESEARCH he that the f the AIDS virus whic AND TREATMENT known asin fingersThere are drues that appear to break iency Syndr number of people infected with the causative virus of the sy e who di various consequence: In the 1980s and 1990s.re s were able to estab AIDS zine finger strategy will have to be made very specific been directed towards How ever.this opti thes une system du king ways by targe tins what is called cell-mediated which is activated followins This type of immunity doe not prevent infection,but rathe ald be ded to nd enb ity of the however.the encouraging.However,studies must still
WORLD OF MICROBIOLOGY AND IMMUNOLOGY AIDS, recent advances in research and treatment 9 • • brings about a greater increase of antibodies and a greater decrease of fulminant HIV than either type of drug alone. Although patients improve on a regimen of mixed drugs, they are not cured due to the persistence of inactive virus left in the body. Researchers are looking for ways to flush out the remaining HIV. In the battle against AIDS, researchers are also attempting to develop a vaccine. As an adjunct to the classic method of preparing a vaccine from weakened virus, scientists are attempting to create a vaccine from a single virus protein. In addition to treatment, the battle against AIDS includes preventing transmission of the disease. Infected individuals pass HIV-laden macrophages and T lymphocytes in their bodily fluids to others. Sexual behaviors and drug-related activities are the most common means of transmission. Commonly, the virus gains entry into the bloodstream by way of small abrasions during sexual intercourse or direct injection with an infected needle. In attempting to prevent HIV transmission among the peoples of the world, there has been an unprecedented emphasis on public health education and social programs; it is vitally important to increase public understanding of both the nature of AIDS and the behaviors that put individuals at risk of spreading or contracting the disease. See also AIDS, recent advances in research and treatment; Antibody and antigen; Blood borne infections; Centers for Disease Control (CDC); Epidemics, viral; Human immunodeficiency virus (HIV); Immunodeficiency disease syndromes; Immunodeficiency diseases; Immunological analysis techniques; Infection and resistance; Infection control; Latent viruses and diseases; Sexually transmitted diseases; T cells or T lymphocytes; Viral genetics; Viral vectors in gene therapy; Virology; Virus replication; Viruses and responses to viral infection AIDS, RECENT ADVANCES IN RESEARCH AIDS, recent advances in research and treatment AND TREATMENT Acquired Immune Deficiency Syndrome (AIDS) has only been known since the early years of the 1980s. Since that time, the number of people infected with the causative virus of the syndrome and of those who die from the various consequences of the infection, has grown considerably. In the 1980s and 1990s, researchers were able to establish that the principle target for the maladies associated with AIDS is the immune system. Since then, much research has been directed towards pinpointing the changes in the human immune system due to infection, seeking ways of reversing these changes, or supplementing the compromised immune system to hold the infection in check. The particular immune system component that has been implicated in the progression of AIDS is a type of T cell called the CDC4 T cell. This cell, which is activated following recognition of the virus by the immune system, functions in the destruction of the cells that have been infected by the virus. Over time, however, the number of CDC4 cells declines. If the decline decreases the T cell count to below 200 per microliter of blood, the number of infective virus particles goes up steeply and the immune system breaks down. This loss of the ability to fight off foreign organisms leaves the patient open to life-threatening illnesses that normally would be routinely defeated by an unimpaired immune system. Until 2001, the prevailing view was that the decline in the number of CDC4 cells was due to a blockage of new T cell production by the infecting virus. However, the conclusions from studies published in 2001 now indicate that the production of new T cells is not blocked, but rather that there is acceleration in the loss of existing T cells. Even though the result is the same, namely the increased loss of the specialized AIDSfighting T cells, the nature of the decline is crucial to determine in order to devise the most effective treatment strategy. If the reasons for the accelerated loss of the T cells can be determined, perhaps the loss can be prevented. This would better equip patients to fight the infection. Since 1998, a multi-pronged strategy of AIDS therapy has been established. Highly Active Anti-Retroviral Therapy (HAART) consists of administering a “cocktail” of drugs targeted to the AIDS virus to a patient, even when the patient shows no symptoms of AIDS. The drug mixture typically contains a so-called nucleoside analog, which blocks genetic replication, and inhibitors of two enzymes that are critical enzyme in the making of new virus (protease and reverse transcriptase). HAART has greatly reduced the loss of life due to AIDS. But, this benefit has come at the expense of side effects that can often be severe. Also, the treatment is expensive. But now, research published toward the end of 2001 indicates that the use of HAART in a “7-day-on, 7-day-off” cycle does not diminish treatment benefits, but does diminish treatment side effects. Costs of treatment has become more reasonable, as well. Another advancement in AIDS treatment may come from the finding that the inner core of the AIDS virus, which is called the nucleocapsid, is held together by structures known as “zinc fingers.” There are drugs that appear to break apart these supports. This stops the virus from functioning. Furthermore, evidence supports the view that the nucleocapsid does not change much over time. Thus, a drug that effectively targeted the nucleocapsid could be an effective drug for a long time. The drawback to this approach at the present time is that other structures in the body utilize zinc fingers. So, an antiAIDS zinc finger strategy will have to be made very specific. In the mid 1980s, there was great optimism that a vaccine for the AIDS virus would be developed within two years. However, this optimism soon disappeared. In late 2001, however, preliminary clinical trials began on a candidate vaccine. Traditional vaccines rely on the administration of a protein to stimulate the production of an antibody that confers protection against the disease-causing organism. The candidate vaccine works by targeting what is called cell-mediated immunity. This type of immunity does not prevent infection, but rather clears the virus-infected cells out of the body. Such a vaccine would be intended to prolong and enhance the quality of the lives of AIDS-infected people. Studies in monkeys have been encouraging. However, studies must still rule out the possibilwomi_A 5/6/03 1:06 PM Page 9