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Phylogenetic inference in the epidemiologic and evolutionary investigation of HIV-1, HCV and HBV

Sallam, Malik LU (2017)
Abstract
Phylogenetics is defined as the study of evolutionary relatedness among various groups of organisms. The evolutionary and epidemiologic studies of viral infections through molecular phylogenetics can provide exquisite comprehension about the origins, spatiotemporal spread and pathogenesis of human viruses. The aim of the current thesis was to study the genetic diversity, transmission dynamics and evolutionary history of selected human viral epidemics, namely HIV-1 in Iceland, HIV-1 in the Middle East and North Africa (MENA), HCV in Southern Sweden and genotype A of HBV around the globe. DNA/RNA purification and PCR amplification followed by population sequencing were utilized to generate viral genomic sequences. The viral sequences were... (More)
Phylogenetics is defined as the study of evolutionary relatedness among various groups of organisms. The evolutionary and epidemiologic studies of viral infections through molecular phylogenetics can provide exquisite comprehension about the origins, spatiotemporal spread and pathogenesis of human viruses. The aim of the current thesis was to study the genetic diversity, transmission dynamics and evolutionary history of selected human viral epidemics, namely HIV-1 in Iceland, HIV-1 in the Middle East and North Africa (MENA), HCV in Southern Sweden and genotype A of HBV around the globe. DNA/RNA purification and PCR amplification followed by population sequencing were utilized to generate viral genomic sequences. The viral sequences were integrated with individual socio-demographic data. State-of-the-art phylogenetic inference methods, including maximum likelihood and Bayesian approaches, were employed to generate the phylogenetic trees that were utilized to classify viral lineages and to infer the putative phylogenetic clusters. For the first time, we described the molecular epidemiology of HIV-1 in Iceland. An increasing trend of genetic diversity of the virus was observed, nevertheless, a few subtypes/circulating recombinant forms (CRFs) dominated the infection there. Injection drug users (IDUs) and men have sex with men were the risk groups mostly affected whereas the transmission among heterosexuals was dependent on interaction with the former risk groups. We managed to uncover the epidemiologic complexion of HIV-1 outbreaks among IDUs in Iceland previously mistaken as a single outbreak by traditional epidemiologic typing. Our results indicated an early date of HIV-1 introduction into the island (1978). Moreover, we found a decreasing prevalence of transmitted drug resistance in Iceland during 1996-2012, with an evidence of local spread of T215C/D dating back to 1989. In the MENA we investigated the HIV-1 transmission phylogenetically for the first time at the regional level. We showed an evidence of substantial proportion of domestic transmission of HIV-1 in the region with indications of different lineage movements across different countries. We also reported a higher proportion of phylogenetic clustering among CRFs compared to pure subtypes in the region. In Southern Sweden, we demonstrated the dominance of four HCV subtypes with IDU as the driving forces of HCV epidemic locally. Dating results pointed to a substantial number of HCV introductions in late 1960s and early 1970s with an indication of ongoing transmission. We identified young age (≤45 years), IDU and sexual transmission, and the HCV subtypes (2b and 3a) as the factors associated with higher likelihood of phylogenetic clustering. In the study of the evolutionary history of genotype A of HBV, preliminary analyses revealed an evidence of recent diversification and spread of the virus worldwide, with indications of the involvement of similar factors that resulted in the pandemic spread of HIV-1. Despite the continued efforts to improve means of treatment and prevention of HIV-1, HCV and HBV, the huge burden of these viral infections requires better understanding of the dynamics of spread and the factors that are associated with higher likelihood of forward transmission of these viruses. The transmission dynamics studies of viral infections could help to increase the efficiency of public health control measures by giving detailed depiction of the variables implicated in virus spread with subsequent focused intervention measures. (Less)
Please use this url to cite or link to this publication:
author
supervisor
opponent
  • PhD, Assistant Professor Hué, Stéphane, London School of Hygiene & Tropical Medicine, London, UK
organization
publishing date
type
Thesis
publication status
published
subject
keywords
HIV, Hepatitis C virus, Hepatitis B virus, Molecular epidemiology, Transmission, Genetic diversity, Phylogeny, Evolution, Human immunodeficiency virus type 1
pages
140 pages
publisher
Lund University, Faculty of Medicine
defense location
BMC, I-huset, lokal 1345, Sölvegatan 19, Lund.
defense date
2017-09-13 09:00
ISBN
978-91-7619-497-3
language
English
LU publication?
yes
id
6b2740d8-5955-4553-a638-094766553cb8
date added to LUP
2017-07-19 13:53:16
date last changed
2017-08-04 09:09:37
@phdthesis{6b2740d8-5955-4553-a638-094766553cb8,
  abstract     = {Phylogenetics is defined as the study of evolutionary relatedness among various groups of organisms. The evolutionary and epidemiologic studies of viral infections through molecular phylogenetics can provide exquisite comprehension about the origins, spatiotemporal spread and pathogenesis of human viruses. The aim of the current thesis was to study the genetic diversity, transmission dynamics and evolutionary history of selected human viral epidemics, namely HIV-1 in Iceland, HIV-1 in the Middle East and North Africa (MENA), HCV in Southern Sweden and genotype A of HBV around the globe. DNA/RNA purification and PCR amplification followed by population sequencing were utilized to generate viral genomic sequences. The viral sequences were integrated with individual socio-demographic data. State-of-the-art phylogenetic inference methods, including maximum likelihood and Bayesian approaches, were employed to generate the phylogenetic trees that were utilized to classify viral lineages and to infer the putative phylogenetic clusters. For the first time, we described the molecular epidemiology of HIV-1 in Iceland. An increasing trend of genetic diversity of the virus was observed, nevertheless, a few subtypes/circulating recombinant forms (CRFs) dominated the infection there. Injection drug users (IDUs) and men have sex with men were the risk groups mostly affected whereas the transmission among heterosexuals was dependent on interaction with the former risk groups.  We managed to uncover the epidemiologic complexion of HIV-1 outbreaks among IDUs in Iceland previously mistaken as a single outbreak by traditional epidemiologic typing. Our results indicated an early date of HIV-1 introduction into the island (1978). Moreover, we found a decreasing prevalence of transmitted drug resistance in Iceland during 1996-2012, with an evidence of local spread of T215C/D dating back to 1989. In the MENA we investigated the HIV-1 transmission phylogenetically for the first time at the regional level. We showed an evidence of substantial proportion of domestic transmission of HIV-1 in the region with indications of different lineage movements across different countries. We also reported a higher proportion of phylogenetic clustering among CRFs compared to pure subtypes in the region. In Southern Sweden, we demonstrated the dominance of four HCV subtypes with IDU as the driving forces of HCV epidemic locally. Dating results pointed to a substantial number of HCV introductions in late 1960s and early 1970s with an indication of ongoing transmission. We identified young age (≤45 years), IDU and sexual transmission, and the HCV subtypes (2b and 3a) as the factors associated with higher likelihood of phylogenetic clustering. In the study of the evolutionary history of genotype A of HBV, preliminary analyses revealed an evidence of recent diversification and spread of the virus worldwide, with indications of the involvement of similar factors that resulted in the pandemic spread of HIV-1. Despite the continued efforts to improve means of treatment and prevention of HIV-1, HCV and HBV, the huge burden of these viral infections requires better understanding of the dynamics of spread and the factors that are associated with higher likelihood of forward transmission of these viruses. The transmission dynamics studies of viral infections could help to increase the efficiency of public health control measures by giving detailed depiction of the variables implicated in virus spread with subsequent focused intervention measures.},
  author       = {Sallam, Malik},
  isbn         = {978-91-7619-497-3},
  keyword      = {HIV,Hepatitis C virus,Hepatitis B virus,Molecular epidemiology,Transmission,Genetic diversity,Phylogeny,Evolution,Human immunodeficiency virus type 1},
  language     = {eng},
  pages        = {140},
  publisher    = {Lund University, Faculty of Medicine},
  school       = {Lund University},
  title        = {Phylogenetic inference in the epidemiologic and evolutionary investigation of HIV-1, HCV and HBV},
  year         = {2017},
}