PhD / HIV-1 is the cause of the majority of global HIV infections. Not only being more virulent, and relatively easily transmitted than HIV-2, HIV-1 is also more extensively studied. HIV-1 is known for its highly recombinogenic nature, together with an extreme genetic variety, both attributable to an error-prone reverse transcriptase which gives rise to heterozygous virion. Sequence diversity of HIV-1 has resulted in identification of 9 subtypes of HIV-1 M group, as well as 43 circulating and a number of other unique recombinant forms of HIV-1. The extensive heterogeneity of HIV-1 has become the main consideration in vaccine development, mainly due to the inherent variability of HIV-1 and the frequent generation of new recombinant forms, which subsequently makes the effort to control the HIV-1 pandemic more challenging. The inter-subtype recombination event is a common phenomenon observed in Malaysia whereby there is a co-circulation of multiple HIV-1 subtypes; CRF01_AE and subtype B. Therefore, it becomes crucial to widen the knowledge of currently emerging CRF01_AE/B inter-subtype recombinants, in order to assist the future regional vaccine design and also to prevent wider spread of these strains. Concurrently, with a better understanding on the characteristics of HIV-1 CRF01_AE/B recombinant forms, further diversification of these strains can possibly be thwarted. The objectives of this study included, firstly to study the molecular epidemiology pattern of different HIV-1 strains, as well as to observe their frequency and distribution. Our second aim was to identify possible derivative from CRF33_01B, and also other new CRF01_AE/B inter-subtype recombinant forms in Malaysia. Thirdly, we aimed to identify possible biological advantages of the CRF33_01B isolates over its parental strains; CRF01_AE and subtype B. Currently, the HIV-1 epidemic in Malaysia is in a concentrated phase with evidence of predominance of both CRF01_AE and subtype B found among heterosexuals and injecting drug users, respectively. There is urgent necessity to apply a more detailed and continuous molecular characterization and epidemiological monitoring of these recombinant forms in Malaysia. We obtained plasma samples from 115 HIV-1-infected patients who attended HIV clinic at the University Malaya Medical Centre in Kuala Lumpur, Malaysia. The HIV-1 PR-RT, gp120-env and gp41-env genes were amplified and sequenced from 50 samples, while the remaining 65 samples were successfully studied at either one or two HIV-1 specific genomic regions. Cloning, phylogenetic analyses, together with bootscanning methods were employed to assign subtypes and to identify inter-subtype recombination based on all three genomic regions. From the plasma-derived sequences of 50 patients, 46% were found to harbour CRF01_AE, 10% and 6% had subtype B and B’, and a total of 18% of the patients were infected with CRF33_01B, while the remaining 18% of patients was found to have unique recombinant forms. As for the other 65 patients, majority of them harboured CRF01_AE and subtype B. This study shows that co-circulation of multiple HIV-1 subtypes and their recombinant strains are frequent in the Malaysian population, while capable of spreading to different HIV-1 risk groups. Possible recombination hotspots in CRF01_AE/B recombinants are suggested to be within the HIV-1 PR-RT gene region. Further, this study highlights the need to characterize and monitor the molecular epidemiology of these recombinant forms. The ideal environment for the inter-subtype recombination event to take place is created by the co-circulation and dual infections of both CRF01_AE and subtype B. With more HIV-1 CRF01_AE/B recombinant forms emerging and shaping the nature of HIV epidemic in Malaysia, certainly it will complicate the timely diagnosis of these molecularly altered HIV-1 forms. The recent identification of the novel CRF33_01B suggests the emergence of other new CRF01_AE/B inter-subtype recombinant forms in Malaysia, as preliminarily demonstrated in some HIV-1 patients identified in the first part of this study. The peripheral blood mononuclear cells (PBMCs) of these HIV-1 patients were co-cultured with those of healthy donors, which we then isolated the proviral genomic DNA. The nested long-range PCR was performed to obtain seven overlapping viral genome fragments that made up the whole viral genome. The detailed phylogenetic, as well as bootscan analyses confirmed the mosaic compositions and recombinant structures of the newly emerging CRF01_AE/B recombinant forms derived from CRF01_AE and subtype B. One of them in particular; HIV-1 isolate 06MYKLD46 is structurally similar to CRF33_01B, except for an extra subtype B fragment within the env region. It also has close phylogenetic relationship and similar breakpoints with CRF33_01B, mainly at the PR-RT region. Furthermore, the other three distinct HIV-1 recombinants; isolates 07MYKLD47, 07MYKLD48 and 07MYKLD49 also display near full-length genomes composed of the backbone of CRF01_AE, with insertions of subtype B fragments at different gene regions. These results indicate the high possibility of second generation of minor recombinant forms derived from CRF33_01B, as well as the continuous evolution and rapid dispersal of CRF01_AE/B recombinants in Malaysia. The high prevalence of newly emerging CRF33_01B (CRF01_AE/B inter-subtype recombinant) may cause a possible epidemiologic shift, attributable to its altered virologic characteristics and possible transmission advantages compared to its parental strains. Two major determinants; the viral factor and host factor have influenced the progress of a productive HIV-1 infection upon virus entry into the host cells. We have assessed the two main viral factors; the in vitro viral replication capacity and the viral fitness of the circulating HIV-1 strains in Malaysia. We have determined that CRF33_01B primary isolate (07MYKLVik) replicates better in activated whole PBMCs and CD4+ T-lymphocytes and is ‘fitter’ than one of its parental strain; CRF01_AE (07MYKLNBL) but not subtype B (07MYKLAfik). Subtype B has more advanced ability to produce a progressive infection in all cell types, including MDMs, and has a comparable viral fitness to that of CRF33_01B. We also investigated the role of host factors in a productive HIV-1 infection, by determining the viral effect on the host cell morphological features. We found that CRF33_01B (07MYKLVik) culture displayed more large syncytia (multinucleated giant cells) with multiple nuclei compared to subtype B (07MYKLAfik) culture, while no snycytia was observed in CRF01_AE (07MYKLNBL) culture. Generally, the cells within CRF33_01B and subtype B cultures appeared to be morphologically distinct from CRF01_AE cultures. This may indicate a more productive HIV-1 infection of CRF33_01B and subtype B, similar to our finding from the in vitro viral replicative capacity and viral fitness assays of these HIV-1 strains. We also studied the effect of different HIV-1 strain infections on host differential gene expression profiles, by using the PCR Array, which detects a total of 84 genes known to be involved in the host response to HIV-1 infection. It was observed that the in vitro infection with CRF33_01B isolates resulted in a more damaging effect on host cells and caused more apoptotic death within the infected cultures, compared to the isolates of its parental subtypes. Moreover, subtype B isolates resulted in a poorer cell response upon viral infection, compared to CRF01_AE/B isolate. Concurrently, it also gave less productive spread of viral infection within the infected cultures, in comparison to CRF01_AE/B isolate. We speculate that if the same scenario is reflected in vivo, CRF01_AE/B inter-subtype recombinant including CRF33_01B would have a better survival rate within the host upon their infection, in comparison to their parental strains. This again strengthens our presumption that CRF33_01B has potential ability to disseminate widely in the Malaysian population and gives a progressive change of the current molecular epidemiological trend by gradually replacing the current predominance of CRF01_AE in the country.

synopsis This dissertation examines the erosion of minority rights in Malaysia through the implementation of special measures in favour of the majority Malays. This dissertation will consider the appropriateness, effectiveness and legitimacy of these special measures under cunent international law standards. This involves a comparison of Malaysia's constitutional, legislative and statutory provisions with international principles of customary and treaty law, and applicable regional declarations. This dissertation will conclude by recommending appropriate policy and legislative reform, if such measures are found to be appropriate in the circumstances. Preamble Malaysia achieved independence fiom Britain on 31 August 1957. The Merdeka Independence Proclamation declared that the nation was to be 'founded upon the principle of liberty and justice and ever seeking the welfare and happiness of its people'. Insightful words for a nation built upon by racial, cultural and religious separatism, as the term 'its people' was presumably meant to encompass both the majority Malays as well as all ethnic minorities.' Unfortunately, the sentiment expressed in the Merdeka proclamation was marred by ethnic polarisation and its resultant ethnocentric legal and political system. The reasons for this will be explored in chapter one, which considers Malaysia's historical and cultural development and the eventual mass pluralisation of Malaysia without a unifying national identity. An understanding of the formation of Malaysia's cultural hegemony, and its subsequent ethnic polarisation, is required to appreciate the current status of Malaysia's ethnic minorities. Part A will consider in detail the preferential policies in favour of Malays introduced by the government following the 1969 race riots and the resulting effect this had on the economic, social and cultural rights of non-Malays. The introduction of these policies also led to the implementation of race based quota systems in the education, employment and business sectors. Correspondingly, the socio-economic position of non-Malay minorities have been affected. The legal implications of these policies are discussed in the proceeding chapters and the reasonableness of these policies will be measured against international law standards. To undertake this assessment, Part B discusses the role of international law and examines its implications to Malaysia. It should be noted fiom the outset that although Malaysia is a member State of the United Nations, it has elected not to ratify significant human rights treaties. Given this, chapter two considers the role of customary law as a part of international law and its implications to the observance of fundamental human rights. This chapter aims to establish that Malaysia as a member of the United Nations, and by virtue of customary law, is bound to recognise fundamental human rights. As this dissertation discusses Malaysia's observance of minority rights at international law, part C examines the availability of fundamental human rights to Malaysia's minorities. Part C reconciles Malaysia's pro-Malay preferential policies with minority rights and considers whether minority rights in Malaysia have been eroded through such policies pursuant to international law standards. Chapter four determines whether the language rights of Malaysia's non-bahasa speakers, who also constitute the ethnic minorities, are recognised and protected by Malaysia's national language policy. This chapter also assesses the impact of Malaysia's national language policy and planning on the education and employment rights of non-Malays given the introduction of language based quota systems in both sectors. Chapter five examines the role of Islam in Malaysia and considers the extent of religious freedom available to non-Muslims in Malaysia Chapter six deals with Malaysia's restrictive laws and how these laws were relied on to revise and modify Malaysia's legal system and policies to benefit Malays whilst simultaneously impacting on the civil, political, economic, social and cultural rights of non-Malay minorities. Chapter six also considers the potential risks associated with the government's continued reliance on these restrictive laws to 'control' interethnic tensions. On the assumption that Malaysia has breached relevant international law standards in some instances, part D recommends possible methods of legislative and policy reform which may be adopted by the government to remedy these breaches. Part D is the concluding chapter of this dissertation. In concluding, this dissertation examines the impact of ethnic divisions on social and political policies in Malaysia and considers the extent of government intervention in the economy based on race which has ultimately impacted on the protection and implementation of minority rights in Malaysia. It is the writer's opinion that the source of ethnic conflict lies within the introduction of legal doctrines which are purposellly detrimental to the rights of minorities. Accordingly, the concluding chapter recommends reforms to Malaysia's legal system and policies to rninirnise the risk of an eruption of inter-ethnic tensions. The aim of this dissertation is to demonstrate that Malaysia's politicisation of competing ethnic interests has resulted in the maintenance of preferential policies detrimental to minority rights and contrary to international law.

This is a study of values and identity within the public relations profession in Malaysia. Although the study has a national focus, its implications are global, because its context is created by the intersection of three current areas of debate and examination: I) the renewed focus on Asian values which seeks to articulate Asian values as a way of supporting Asia's pathway to modernisation; 2) the open challenge to assumptions about the transferability of theory between countries around the world, about whether theory can be universal or whether different theories or different versions of theories are needed to help explain practice in different parts of the world; and 3) the reemerging focus on values underwriting the public relations profession. Malaysia's growing public relations profession is playing a crucial communication role in support of the country's move towards industrialisation. In Malaysia, issues of culture, modernisation, Westernisation, and globalisation are both real and topical. Through the values framework, the study aims to contribute in three ways: 1) To develop and test an alternative, but equally useful, framework and method for comparing public relations practice between countries; 2) to investigate the influence of specific cultural and professional variables on public relations practice in Malaysia, to hrther understand specific variables which might lead public relations practice to differ between countries; and 3) to contribute to the definition of Asian values by defining one component, that is, the personal and professional values of a sample of public relations practitioners in Malaysia. The research was undertaken in two parts. The first, using a survey and structured interviews, examined the influence of two cultural variables (ethnicity and gender) and two professional variables (years of experience and work environment) on values held. Ethnicity and years of experience led to significant differences in the values held, with each variable influencing different value dimensions. Gender and work environment had some influence but generally in combination with ethnicity and years of experience respectively. The study found a distinctive U-shaped curve related to years of experience, which means that practitioners' value priorities change as they gain more experience in the profession. All four of the variables studied could be significant in accounting for difference in professional practice in other countries. The second part, using repertory grid methodology, examined values and identity. It identified core values central to public relations practice in Malaysia, and interpreted these core values as statements of self-identity. The nature of identity as a public relations practitioner may also account for differences in public relations practice between countries. Combining both parts, the study has revealed values that underwrite public relations practice in Malaysia, the aspects of self-identity important to the profession, and the way in which those values and identity have been influenced by cultural and professional factors. It therefore leads towards the development of a theoretical foundation for "culture-specific" public relations in Malaysia. This exploratory study has generated findings which challenge the expectations of Schwartz and Bilsky's values theory, on which the values analysis was based.

PhD / HIV-1 is the cause of the majority of global HIV infections. Not only being more virulent, and relatively easily transmitted than HIV-2, HIV-1 is also more extensively studied. HIV-1 is known for its highly recombinogenic nature, together with an extreme genetic variety, both attributable to an error-prone reverse transcriptase which gives rise to heterozygous virion. Sequence diversity of HIV-1 has resulted in identification of 9 subtypes of HIV-1 M group, as well as 43 circulating and a number of other unique recombinant forms of HIV-1. The extensive heterogeneity of HIV-1 has become the main consideration in vaccine development, mainly due to the inherent variability of HIV-1 and the frequent generation of new recombinant forms, which subsequently makes the effort to control the HIV-1 pandemic more challenging. The inter-subtype recombination event is a common phenomenon observed in Malaysia whereby there is a co-circulation of multiple HIV-1 subtypes; CRF01_AE and subtype B. Therefore, it becomes crucial to widen the knowledge of currently emerging CRF01_AE/B inter-subtype recombinants, in order to assist the future regional vaccine design and also to prevent wider spread of these strains. Concurrently, with a better understanding on the characteristics of HIV-1 CRF01_AE/B recombinant forms, further diversification of these strains can possibly be thwarted. The objectives of this study included, firstly to study the molecular epidemiology pattern of different HIV-1 strains, as well as to observe their frequency and distribution. Our second aim was to identify possible derivative from CRF33_01B, and also other new CRF01_AE/B inter-subtype recombinant forms in Malaysia. Thirdly, we aimed to identify possible biological advantages of the CRF33_01B isolates over its parental strains; CRF01_AE and subtype B. Currently, the HIV-1 epidemic in Malaysia is in a concentrated phase with evidence of predominance of both CRF01_AE and subtype B found among heterosexuals and injecting drug users, respectively. There is urgent necessity to apply a more detailed and continuous molecular characterization and epidemiological monitoring of these recombinant forms in Malaysia. We obtained plasma samples from 115 HIV-1-infected patients who attended HIV clinic at the University Malaya Medical Centre in Kuala Lumpur, Malaysia. The HIV-1 PR-RT, gp120-env and gp41-env genes were amplified and sequenced from 50 samples, while the remaining 65 samples were successfully studied at either one or two HIV-1 specific genomic regions. Cloning, phylogenetic analyses, together with bootscanning methods were employed to assign subtypes and to identify inter-subtype recombination based on all three genomic regions. From the plasma-derived sequences of 50 patients, 46% were found to harbour CRF01_AE, 10% and 6% had subtype B and B’, and a total of 18% of the patients were infected with CRF33_01B, while the remaining 18% of patients was found to have unique recombinant forms. As for the other 65 patients, majority of them harboured CRF01_AE and subtype B. This study shows that co-circulation of multiple HIV-1 subtypes and their recombinant strains are frequent in the Malaysian population, while capable of spreading to different HIV-1 risk groups. Possible recombination hotspots in CRF01_AE/B recombinants are suggested to be within the HIV-1 PR-RT gene region. Further, this study highlights the need to characterize and monitor the molecular epidemiology of these recombinant forms. The ideal environment for the inter-subtype recombination event to take place is created by the co-circulation and dual infections of both CRF01_AE and subtype B. With more HIV-1 CRF01_AE/B recombinant forms emerging and shaping the nature of HIV epidemic in Malaysia, certainly it will complicate the timely diagnosis of these molecularly altered HIV-1 forms. The recent identification of the novel CRF33_01B suggests the emergence of other new CRF01_AE/B inter-subtype recombinant forms in Malaysia, as preliminarily demonstrated in some HIV-1 patients identified in the first part of this study. The peripheral blood mononuclear cells (PBMCs) of these HIV-1 patients were co-cultured with those of healthy donors, which we then isolated the proviral genomic DNA. The nested long-range PCR was performed to obtain seven overlapping viral genome fragments that made up the whole viral genome. The detailed phylogenetic, as well as bootscan analyses confirmed the mosaic compositions and recombinant structures of the newly emerging CRF01_AE/B recombinant forms derived from CRF01_AE and subtype B. One of them in particular; HIV-1 isolate 06MYKLD46 is structurally similar to CRF33_01B, except for an extra subtype B fragment within the env region. It also has close phylogenetic relationship and similar breakpoints with CRF33_01B, mainly at the PR-RT region. Furthermore, the other three distinct HIV-1 recombinants; isolates 07MYKLD47, 07MYKLD48 and 07MYKLD49 also display near full-length genomes composed of the backbone of CRF01_AE, with insertions of subtype B fragments at different gene regions. These results indicate the high possibility of second generation of minor recombinant forms derived from CRF33_01B, as well as the continuous evolution and rapid dispersal of CRF01_AE/B recombinants in Malaysia. The high prevalence of newly emerging CRF33_01B (CRF01_AE/B inter-subtype recombinant) may cause a possible epidemiologic shift, attributable to its altered virologic characteristics and possible transmission advantages compared to its parental strains. Two major determinants; the viral factor and host factor have influenced the progress of a productive HIV-1 infection upon virus entry into the host cells. We have assessed the two main viral factors; the in vitro viral replication capacity and the viral fitness of the circulating HIV-1 strains in Malaysia. We have determined that CRF33_01B primary isolate (07MYKLVik) replicates better in activated whole PBMCs and CD4+ T-lymphocytes and is ‘fitter’ than one of its parental strain; CRF01_AE (07MYKLNBL) but not subtype B (07MYKLAfik). Subtype B has more advanced ability to produce a progressive infection in all cell types, including MDMs, and has a comparable viral fitness to that of CRF33_01B. We also investigated the role of host factors in a productive HIV-1 infection, by determining the viral effect on the host cell morphological features. We found that CRF33_01B (07MYKLVik) culture displayed more large syncytia (multinucleated giant cells) with multiple nuclei compared to subtype B (07MYKLAfik) culture, while no snycytia was observed in CRF01_AE (07MYKLNBL) culture. Generally, the cells within CRF33_01B and subtype B cultures appeared to be morphologically distinct from CRF01_AE cultures. This may indicate a more productive HIV-1 infection of CRF33_01B and subtype B, similar to our finding from the in vitro viral replicative capacity and viral fitness assays of these HIV-1 strains. We also studied the effect of different HIV-1 strain infections on host differential gene expression profiles, by using the PCR Array, which detects a total of 84 genes known to be involved in the host response to HIV-1 infection. It was observed that the in vitro infection with CRF33_01B isolates resulted in a more damaging effect on host cells and caused more apoptotic death within the infected cultures, compared to the isolates of its parental subtypes. Moreover, subtype B isolates resulted in a poorer cell response upon viral infection, compared to CRF01_AE/B isolate. Concurrently, it also gave less productive spread of viral infection within the infected cultures, in comparison to CRF01_AE/B isolate. We speculate that if the same scenario is reflected in vivo, CRF01_AE/B inter-subtype recombinant including CRF33_01B would have a better survival rate within the host upon their infection, in comparison to their parental strains. This again strengthens our presumption that CRF33_01B has potential ability to disseminate widely in the Malaysian population and gives a progressive change of the current molecular epidemiological trend by gradually replacing the current predominance of CRF01_AE in the country.

Thesis (MA)--University of Stellenbosch, 2006. / Bibliography. Also available via the Internet.

Zugl.: Heidelberg, Univ., Diplomarbeit, 2005 / Titel auf der Beil.

University, Diss., 2005--Kiel.

Diss. (sammanfattning) Uppsala : Sveriges lantbruksuniv., 2004. / Härtill 6 uppsatser.

Thesis (Ph. D.)--Princeton University, 1998. / Includes bibliographical references (leaves 482-508).

Thesis (Ph.D.)--Emory University, 2005. / "UMI Number: 3201416"--T.p. verso. Includes bibliographical references (p. 472-489).