HIV-1 is divided into three groups: Group M (for major), Group O (for outlier) and Group N(for non-M, non-O strains).
■ Group M virusesare separated into ten different subtypes (clades) distinguished by capital alphabetical letters A to J.
■ Group O virusesconsist of a pool of highly divergent, genetically related strains with no defined subtypes.
■ Those rare (but increasingly being identified) variants of HIV that cannot be assigned to either group are now designated as Group N viruses.27
Individual subtypes may be associated with different transmission potentials and differences in virulence between HIV-1 variants.27
In some regions of the world, a specific subtype can be identified as the dominant clade infecting most people. For example, in North America, Western Europe and East Asia, HIV-1 Group M clade B is the dominant subtype, while in Thailand it is HIV-HIV-1 Group M clade E, and clade C predominates in Southern Africa, the Horn of Africa and West Asia. In some regions, mixtures of clades are found, e.g. Eastern Europe and sub-Saharan Africa.28Most subtypes are found in Africa, as you would expect, as this was the origin of HIV.
Because HIV-1 Group O differs significantly from HIV-1 Group M clades, infection with this variant was not always detected by some HIV antibody tests. In the past, this represented a potential risk to public health, particularly in relation to maintaining the safety of blood products. However, all current assays have now been modified to take account of Group O strains. Antibody tests may not, however, detect the more rarely occurring Group N strains
of HIV-1. It is probable that other variants of HIV may emerge, and medical scientists all over the world are engaged in co-operative, active surveillance for the early detection of new variants and the appropriate modification of test kits so that all HIV variants can be serologically identified.
Subtypes have also been recognized and described for HIV-2 (designated A to E), but these have been based on studies of limited number of isolates.19
Summary
Until relatively recently, retroviruses were thought to cause disease only in animals, not humans. Following the recognition of AIDS in 1981, scientists in France and the USA quickly identified new retroviruses that caused fatal lesions in the immune system that led to the development of AIDS, and in time these viruses became known as HIV-1 and HIV-2. In this chapter, we have reviewed the biological characteristics of HIV, including the genetic structure of the RNA viral genome. We have also noted the functions of viral enzymes such as reverse transcriptase, integrase and protease and their role in viral replication. Additionally, we discussed the origins of HIV, compared and contrasted HIV-1 and HIV-2, and finally focused on the diversity of these viruses, both in individuals with the development of quasispecies, and geographical diversity, with the development of different groups and subtypes of HIV.
REFERENCES
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4. Levy JA, Hoffman AD, Kramer SM et al. Isolation of lymphocytopathic retroviruses from San Francisco patients with AIDS. Science 1984; 225:840–2.
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6. Rous P. A sarcoma of the fowl transmissible by an agent separable from the tumor cells.
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Prologue to Chapter 4
Having acquired a general understanding of the biology of HIV, in the following chapter we will review how these viruses are transmitted from person to person and examine the diverse vulnerabilities to infection among individuals and communities. We will further extend our understanding of basic retrovirology in Chapter 6, when we explore the pathogenesis of HIV disease, that is, the calamitous impact HIV has on the immune system and individual health.
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8. Kalyanaraman VS, Sarngaddharan MG, Robert-Gurogg M et al. A new subtype of human T-cell leukemia virus (HTLV-II) associated with a T-cell variant of hairy cell leukemia. Science 1982; 218:571–3.
9. Gallo RC, Essex M, Gross L. Human T-cell Leukemia/Lymphoma Virus. Cold Spring Harbor, NY: Cold Spring Harbor Press, 1982.
10. Clavel F, Guétard D, Brun-Vézinet F et al. Isolation of a new human retrovirus from West African patients with AIDS. Science 1986; 233:343–6.
11. Essex M. Origin of acquired immunodeficiency syndrome. In: DeVita VT Jr, Hellman S, Rosenberg SA (eds), AIDS: Etiology, Diagnosis, Treatment and Prevention, 4th edn.
Philadelphia: JB Lippincott-Raven, 1997, 3–14.
12. Stevenson M. Viral genes and their products. In: Merigan TC Jr, Bartlett JG, Bolognesi D (eds), Textbook of AIDS Medicine, 2nd edn. Baltimore: Williams & Wilkins, 1999, 23–48.
13. Pavlakis GN. The molecular biology of human immunodeficiency virus type 1. In:
DeVita VT Jr, Hellman S, Rosenberg SA (eds), AIDS: Etiology, Diagnosis, Treatment and Prevention, 4th edn. Philadelphia: JB Lippincott-Raven, 1997, 45–74.
14. Geleziunas R, Greene WC. Molecular insights into HIV-1 infection and pathogenesis.
In: Sande MA, Volberding PA (eds), The Medical Management of AIDS, 5th edn.
Philadelphia: WB Saunders Co., 1999, 22–39.
15. Nahmias AJ, Weiss J, Yao X et al. Evidence for human infection with an HTLV-III/LAV-like virus in Central Africa, 1959. Lancet 1986; I:279.
16. Zhu T, Ho D, Nahmias A. An African HIV-1 sequence from 1959 and implications for the origin of the epidemic. Nature 1998; 391:531–2.
17. Weiss RA. Polio vaccines exonerated. Nature 2001; 410:1035–6.
18. Barin F, M’Boup S, Denis F et al. Serological evidence for virus related to simian T-lymphotropic retrovirus III in residents of West Africa. Lancet 1985; ii:1387–9.
19. Essex M, Kanki PJ. Human immunodeficiency virus type 2 (HIV-2). In: Merigan TC Jr, Bartlett JG, Bolognesi D (eds), Textbook of AIDS Medicine, 2nd edn. Baltimore:
Williams & Wilkins, 1999, 985–1001.
20. Hahn B. The origin of HIV-1: a puzzle solved? 6th Conference on Retroviruses and Opportunistic Infections, Chicago, IL, January 31–February 4, 1999, Abst S2.
21. Gao F, Bailes E, Robertson DL et al. Origin of HIV-1 in the chimpanzee Pan troglodytes troglodytes. Nature 1999; 397:436–41.
22. Hirsch VM, Olmsted RA, Murphey-Corb M, Purcell RH, Johnson PR. An African primate lentivirus (SIVsm) closely related to HIV-2. Nature 1989; 339:389–92.
23. Hu DJ, Dondero TJ, Mastro TD, Gayle HD. Global and molecular epidemiology of HIV. In: Wormser GP (ed.), AIDS and Other Manifestations of HIV Infection, 3rd edn.
Philadelphia: Lippincott-Raven, 1998, 27–40.
24. Kanki PJ. Virologic and biologic features of HIV-2. In: Wormser GP (ed.), AIDS and Other Manifestations of HIV Infection, 3rd edn. Philadelphia: Lippincott-Raven,1998, 161–73.
25. Coffin JM. Genetic diversity and evolution of retroviruses. Current Topics in Medical Immunology 1992; 176:143–64.
26. Eigen M. Viral quasispecies. Scientific American 1993; 269:42–9.
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28. Burke DS, McCutchan FE. Global distribution of human immunodeficiency virus-1 clades. In: DeVita VT Jr, Hellman S, Rosenberg SA (eds), AIDS: Etiology, Diagnosis, Treatment and Prevention, 4th edn. Philadelphia: JB Lippincott-Raven, 1997, 119–26.
FURTHER READING
Coffin JM. Retrovirology: an overview. In: Wormser GP (ed.), AIDS and Other
Manifestations of HIV Infection, 3rd edn. Philadelphia: Lippincott-Raven, 1998, 41–121, ISBN 0-397-58760-0.
Collier L, Oxford J. Human Virology, 2nd edn. Oxford: Oxford University Press, 2000, 284 pp, ISBN 0-19-262820-8.
Weiss RA, Wain-Hobson S (eds). Origins of HIV and the AIDS epidemic. Papers of a Discussion Meeting. Philosophical Transactions of The Royal Society 29 June 2001;
356:777–977. Available from The Royal Society, 6 Carlton House Terrace, London SW1Y 5AG, UK; e-mail: [email protected] or from the website:
www.pubs.royalsoc.ac.uk
INTERNET RESOURCES
■ To review an animated version of HIV replication, visit Roche Pharmaceuticals’ HIV Focus website on:
http://www.roche-hiv.com
Internet resources 31
HIV transmission
In this global emergency, prevention of HIV infection must be our greatest worldwide public health priority. Science will one day triumph over AIDS, just as it did over smallpox. Curbing the spread of HIV will be the first step. Until then, reason, solidarity, political will and courage must be our partners.
The Durban Declaration 2000 South Africa1
Learning outcomes
After studying and reflecting on the material in this chapter, you will be able to:
■ describe the principal means by which people become exposed to and infected with HIV;
■ identify risk factors associated with each of these transmission categories;
■ discuss the varying patterns of HIV transmission in different regions of the world.
Introduction
The continuing perpetuation of the global pandemic of HIV disease and the ever-increasing incidence of new HIV infections every year throughout the world, as reviewed in Chapter 1, are inextricably linked to the different ways in which this virus is transmitted among people. Understanding the means by which people can become exposed to and infected with HIV is central to developing strategies for patient education focused on primary prevention. In this chapter we explore these different domains of exposure and the risk factors in each domain associated with an increased vulnerability for HIV infection in both individuals and communities.