HIV as a Successful Pathogen

Introduction

            In 1981, a cluster of cases of Pneumocytis pneumonia appeared in the Los Angeles area. This extremely rare disease was usually seen only in persons who were immunosuppressed. Investigators soon correlated the appearance of this disease with an unusual incidence of a rare form of cancer of the skin and blood vessels called Kaposi’s sarcoma. The people affected were all young homosexual men, and all showed loss of immune function. By 1983, the pathogen causing the loss of immune function had been identified as a retrovirus that selectively infects certain T cells. This virus is now known as human immunodeficiency virus (HIV) (Strohman, 2003).

            There have been several theories about the origin of HIV. It is now believed that it arose by mutation of a virus that had been endemic in some areas of central Africa for many years. The virus has been found in blood samples preserved from as early as 1959 in several African nations and in England.

            Thesis Statement: This paper investigates why HIV is such a successful pathogen and knows some vaccine and treatments of HIV.

1. Methodology

            In order to accomplish this study, the researcher used two different methods to make the investigation more informative, accurate, and successful. Aside from gathering information through internet, the researcher gathered information through statistics and observation.

III. Literature Review

1. Opportunistic Organisms

            Although it is convenient to categorize symbiotic relationship by type, we must keep in mind that under certain conditions the relationship can change. For example, given proper circumstances, a mutualistic organism, such as E. coli, can become harmful. E. coli is generally harmless as long as it remains in the large intestine. But if it gains access to other body sites, such as the urinary bladder, lungs, spinal cord, or wounds, it may cause urinary tract infections, pulmonary infections, meningitis, or abscesses, respectively (“AIDS.” Science 239:573-623, February 5, 2001).

             Opportunists are potentially pathogenic organisms that ordinarily do not cause disease in their normal habitat in a healthy person. For example, organisms that gain access through broken skin or mucous membranes can cause opportunistic infections. Tooth decay and gum disease are caused by bacteria that are considered members of the normal flora of the mouth. Or, if the host is already weakened or compromised by infection, microbes that are usually harmless can cause disease. The disease AIDS is often accompanied by a common opportunistic infection, Pneumocystis pneumonia, caused by the opportunistic organism Pneumocystis carinii. This secondary infection can develop in AIDS sufferers because their immune systems are suppressed (“AIDS.” Science 239:573-623, February 5, 2001). Prior to the AIDS epidemic, this type of pneumonia was rare.

            In addition to the usual symbionts, many people carry other microorganisms that are generally regarded as pathogenic but that may not cause disease in those people. Among the pathogens that are frequently carried in normal individuals are echoviruses (“echo” comes enteric cytopathogenic human orphan), which can cause intestinal diseases, and adenoviruses, which can cause respiratory diseases. Neisseria meningitides, which often resides benignly in the respiratory tract, can cause meningitis, a disease that inflames the coverings of the brain and spinal cord. Streptococcus pneumoniae, a normal resident of the nose and throat, can cause a type of pneumonia (King, 2003).

1. Discussion
2. HIV as a successful pathogen

            HIV infects helper T cells named T4 cells (for the DC4 antigen on their surface). Once inside the infected cell, the viral RNA is transcribed into DNA that remains incorporated into the genetic material of that cell. HIV may remain latent in the cell or begin replicating. Sometimes, replication results in continuous production of new virus particles that bud from the cell without killing it and infect other cells. In other cases, the cell is quickly killed either by the virus itself or by the action of the immune system in response to viral antigens on the surface of the cell. The virus also infects other types of cells that carry DC4 surface antigens. These cells include macrophages, antigen-presenting dendritic cells, about 40% of all monocytes, and 5% of B cells. HIV infection generally does not kill these cells but impairs their normal functioning (“What science knows about AIDS.” Scientific American 259 (4), October 2000.).

            The ability of the virus to remain latent intracellularly is one reason why the anti-HIV antibodies developed by infected persons fail to prevent the disease. The virus also evades immune defenses by undergoing antigenic changes, even during the course of an infection. There is evidence that a change of a single amino acid in the glycoprotein envelope of the virus may enable it to avoid antibodies against the previous antigenic configuration. HIV also evades the immune system by staying in vesicles within cells so that viral antigens are not displayed on the cell surface and T cells cannot detect the infected cells. Moreover, infected cells displaying viral antigens can fuse to uninfected cells to spread the virus.

            AIDS is actually only the end stage of an infection by HIV. Shortly after the initial infection, the patient undergoes seroconversion—that is, tests positive for antibodies to HIV. This interval is almost always less than six months. The symptoms at this point are absent or resemble mononucleosis—a mild fever, swollen lymph nodes, and fatigue. Even these symptoms spontaneously disappear in a few weeks (“What science knows about AIDS.” Scientific American 259 (4), October 2000.).

            Chronic lymphadenopathy (swollen lymph nodes) usually announces the beginning of stage 2 and is often the first indication of illness. This stage lasts for several years; the patient does not feel especially unwell, but the number of T4 cells in the circulation declines steadily. Stage 3 is signaled by a T4 count below 400 per milliliter, and stages 4 and 5 are measured by evidence of progressive loss of effective immune response. The evidence includes loss of ability to respond to certain hypersensitivity tests and development of disease conditions such as an overgrowth by the fungus Candida albicans. Stage 6 of the infection is the disease condition actually called AIDS; the T4 cell count falls below 100 per milliliter and the patient falls victim to one or several opportunistic infections such as Pneumocystis pneumonia (Gallant, 2001). At the present state of therapy, most persons entering this stage will die within about two years.

            The average time from infection to the development of AIDS is about 10 years. Because of this long incubation period, it is not yet known what percentage of persons infected with HIV will develop full-blown AIDS: present indications are that the great majority will.

Figure 1.1 The HIV virion (cross-section). The protein molecules of the viral envelope form knobs that project outward. Within the spherical capsid is a cone-shaped core that contains two molecules of RNA with a molecule of reverse transcriptase attached to each. Once the RNA enters the host cell, the reverse transcriptase transcribes it into DNA.

            Helper T (T_H) cells play a variety of roles. The cause of the pathogenicity of the AIDS virus was identified by using monoclonal antibodies to show that a certain group of T_H cells was being decimated. These T cells contain a surface antigen called CD4 and are most important in a vigorous immune response. We have already seen that certain T_H cells present T-dependent antigens to B cells. Some other T_H cells help other T cells to respond to antigens (Gallant, 2001).

1. Mode of Transmission

            Transmission of HIV usually requires transfer of bodily fluids. The most important of these are blood, semen, and vaginal secretions that contain the virus, or the transfer of cells, especially macrophages, containing the virus. It has been established that the routes of transmission include intimate sexual contact, breast milk, blood-contaminated needles, and blood-to-blood contact such as transfusions. Heterosexual contact is much more likely to transmit HIV when genital lesions are present. This is considered a very important factor in the spread of AIDS in central Africa, where sexually transmitted diseases that result in such lesions are prevalent. Heterosexual spread in Africa is so common that the male: female ratio among AIDS patients is about 1: 1 as compared with 13: 1 in the United States. Heterosexual transmission is increasing in the United States, however, especially via women who are drug abusers and resort to prostitution to support their addiction. The risk of sexual transmission is minimized by the use of condoms. Saliva may contain the virus, but transmission is not known to occur by kissing. There have been recorded instances, though, of sexual transmission of HIV in persons whose only sexual contacts were oral-genital (AIDS Institute, (2000)

            Worldwide epidemiological studies indicate three geographic patterns of transmission: (1) Transmission is primarily among homosexual or bisexual males and intravenous drug abusers in North America, Western Europe, Australia, and New Zealand. (2) Heterosexual contact is the primary mode of transmission in African and Caribbean countries. (3) Most AIDS cases in Eastern Europe, the Middle East, and Asia have occurred among people who have traveled to endemic areas and had sexual contact with infected homosexual men and female prostitutes. Lax procedures for needle sterilization have resulted in a number of hospital-associated outbreaks of AIDS in the Soviet Union and Romania (AIDS Institute, (2000)

            AIDS is not transmitted by insects or by casual social contact such as hugging and sharing household facilities, drinking glasses, or towels. Transmission by blood transfusion in developed countries is unlikely because blood is tested for AIDS antibodies. However, there will always be a slight risk, because blood might be donated during the interval between infection and appearance of detectable antibodies.  Tests for the virus itself are also available, but they have not proved to be superior in screening blood. There is no risk at all in donating blood. AIDS has been transmitted by organ transplants and artificial insemination with donated sperm. HIV-positive women should not become pregnant because of the probability (at least 30%) of transmitting the virus to the fetus (King, 2003).

1. Vaccines and Treatments

            There are two basic areas of AIDS research. Some researchers are working on vaccines to prevent the disease, and others are looking for drugs to treat AIDS.

• Vaccines

There are great obstacles to production of an AIDS vaccine, among them the lack of a suitable animal host for the virus. However, researchers are now optimistic that a vaccine, once produced, could be effective. One reason for optimism is that a very few persons who were once HIV-positive have spontaneously become HIV-negative, indicating that the immune system is probably capable in rare instances of the virus, many think it unlikely that any whole-virus vaccine, either killed or attenuated, would be acceptable for use on uninfected persons. However, such a vaccine would be acceptable for use in attempting to clear the virus after infection. Most efforts are directed at subunit vaccines based on surface envelope antigens of the virus. However, such vaccines must overcome the problem of many antigenic variants (Strohman, 2003). In addition, an effective vaccine would have to stimulate cell-mediated as well as humoral immunity to deal with HIV contained within macrophages or other cells.

• Chemotherapy  

A promising approach to arresting an HIV infection is to flood the body with artificially produced, soluble CD4-type molecules that would bind to circulating viruses before they could locate a CD4 receptor on a T cell. In early experiments the interceptor CD4 molecules were rapidly degraded, requiring repeated injections at an impractical rate. The double CD4 would have to be modified in some way so as to remain in circulation for an extended time for this approach to be practical (King, 2003).

      Most early anti-HIV drugs such as Zidovudine (AZT) are inhibitors of the enzyme reverse transcriptase. HIV is a retrovirus that copies RNA into DNA. The drugs, mostly analogs of nucleic acids, trick the enzyme into terminating the synthesis of viral DNA. Such drugs have slowed the progress of the disease but have not led to a cure. Other than the reverse transcriptase step, there are at least 13 other points at which the production of HIV could be selectively interrupted by drugs. For example, because it has no equivalent in human cells, an attractive target is the viral enzyme protease. This enzyme cuts proteins into pieces that are then reassembled into new HIV particles. Inhibiting it would prevent viral synthesis (King, 2003). Numerous other approaches are being intensively studied, and the most successful solutions might well be some that are not even anticipated now.

1. Conclusion

            As a conclusion, AIDS poses one of this century’s most formidable health threats, but it is not the first serious epidemic of sexually transmitted disease.The Centers for Disease Control estimate that about 1 million persons in the United States are now infected with HIV and projects that 365, 000 AIDS cases will have been diagnosed in the United States by the end of 2002 and 263, 000 patients will have died by that time. The annual cost for the care of AIDS patients will be in the billions of dollars. Worldwide, the estimates are that there are more than 1 million total cases of AIDS and that 10 million persons are infected.

            The AIDS epidemic gives clear evidence of the value of basic scientific research. It is important to reflect that without the advances of the past few decades in molecular biology, we would have been unable even to identify the agent of AIDS, to develop the tests used to screen donated blood, or to monitor the course of the infection.

Reference:

1. “AIDS.” Science 239:573-623, February 5, 2001. This special issue includes eight articles on AIDS: virus biology, epidemiology, and legal and ethical issues.
2. “What science knows about AIDS.” Scientific American 259 (4), October 2000. This issue is devoted entirely to AIDS. Ten articles cover a wide range of topics, including molecular biology, epidemiology, and treatments.
3. AIDS Institute, (2000). Information update: AIDS Institute discontinues recommendation of intra-vaginal application of N-9 as method of HIV risk reduction. Corning Tower, Albany, NY.
4. Gallant, J. (2001). The seropositive patient: The initial encounter. HIV/AIDS Clinical Management Modules, Medscape, Inc.
5. King, Edward. (2003). Safety in Numbers. London: Cassell.
6. Strohman, Richard C. (2003). Genetic Determinism as a Failing Paradigm in Biology and Medicine: Implications for Health and Wellness. Journal of Social Work Education, Vol. 39.