Global Molecular Epidemiology of HIV: Understanding the Genesis of AIDS Pandemic

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Publisher Summary

This chapter describes the classification and distribution of human immunodeficiency virus (HIV) genotypes and the biological and public health implications of genetic variability of this pathogen. Global dissemination of HIVs represents a dramatic and deadly example of recent genome emergence and expansion. Recent studies revealed that a pandemic HIV strain, HIV‐1 group M, began its expansion in human population during early 20th century, it has been diversifying rapidly, now comprising a number of different subtypes and circulating recombinant forms (CRFs), and that new recombinant strains are arising continually, becoming a powerful force in global HIV‐1 spread. Studies also provide information to delineate the mechanism of viral evolution and for the studies on biological features of HIV strains related to pathogenecity and disease progression. However, the biological significance of the global diversity of HIV‐1 strains remains to be defined. Although the immune correlates for protection are still incompletely understood, the extensive variation of HIVs could probably be important in the formulation of the vaccine immunogens.

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Chapter Overview

Global dissemination of the Human immunodeficiency virus (HIV) represents a dramatic and deadly example of recent genome emergence and expansion. Since HIV‐1 group M began its expansion in human population roughly 70 years ago (in early twentieth century), it has been diversifying rapidly, now comprising a number of different subtypes and circulating recombinant forms (CRFs). Molecular epidemiological method has been useful tool to analyze the origin of HIVs and to track a course of global HIV

HIV Types (HIV‐1 and HIV‐2)

Etiologic agents for AIDS are subdivided into two related human retroviruses (lentiviruses): HIV‐1 (HIV type 1) and HIV‐2 (HIV type 2). HIV‐1 is distributed worldwide, accounting for the majority of HIV infections. By contrast, HIV‐2 is confined to West Africa and southern/western India (Schim van der Loeff et al., 1999). Sporadic occurrences and transmission outbreaks of HIV‐2 have been reported from many European countries (Cilla 2001, Damond 2004) and North and South America (Sullivan et al.

Global HIV‐1 Variability

On a global scale, the most prevalent HIV‐1 genotypes are subtypes C (56%), A (23%), B (8%), D (5%), and CRF01_AE (5%) in 1999 (Esparza and Bhamarapravati, 2000) (Fig. 4). The greatest genetic diversity of HIV‐1 has been found in central Sub‐Saharan Africa. Subtypes A and C are most common, but all groups and subtypes have been identified. The extensive diversification of HIV‐1 group M appears to occur within or near the DRC, where the highest diversity of group M has been recorded (Kalish 2004

Phylogenetic Sequence Analysis

For subtype classification, phylogenetic sequence analysis is the most reliable method. Various software programs for phylogenetic analysis (i.e., molecular evolutionary genetic analysis, MEGA) are freely available (http://hiv‐web.lanl.gov/). Due to the high frequency of recombination in HIV, it is necessary to equip software programs designed for identifying recombination. This is particularly the case for the molecular epidemiological investigation in the areas where different lineages of

HIV/AIDS as a “Zoonosis”

Current evidence indicates that HIV‐1 and HIV‐2 entered into human population through multiple zoonotic infections from SIVs‐infected nonhuman primates (Hahn et al., 2000). It has been known that HIV‐2 and SIV sm have a high degree of genetic and phenotypic homology (Gao et al., 1992), sharing unique open‐reading frame, called vpx, in their genomes. Moreover, the habitat of the sooty mangabey closely matches HIV‐2 endemicity in West Africa. These close relationships between HIV‐2 and SIV‐sm led

HIV‐1 Subtypes and Disease Progression

It has been suggested that HIV‐1 subtypes could influence viral transmissibility and pathogenecity. However, the existence of many other factors makes it difficult to establish the true effect of viral subtypes. A study in Thailand showed that the disease progression in the patients infected with CRF01_AE is similar to those observed in subtype B‐infected populations in the West (Amornkul 1999, Kilmarx 2000).

In contrast, several studies showed that HIV‐1 subtypes differ in rates of progression

Conclusions

Global dissemination of HIVs represents a dramatic and deadly example of recent genome emergence and expansion. As reviewed in this chapter, recent studies revealed that a pandemic HIV strain, HIV‐1 group M, began its expansion in human population roughly 70 years ago (early twentieth century), it has been diversifying rapidly, now comprising a number of different subtypes and CRFs, and that new recombinant strains are arising continually, becoming a powerful force in global HIV‐1 spread.

Acknowledgments

We thank Tee Kok Keng, Shigeru Kusagawa, and Midori Kawasaki for assistance with the manuscript and references, and Drs. Kuan‐Teh Jeang and Naoki Yamamoto for their encouragement and advice. We acknowledge grant support from Ministry of Health, Labour and Welfare, Ministry of Education, Science and Technology in Japan and Japanese Foundation for AIDS Prevention. We also thank our collaborators and colleagues in Asia.

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