Matching Items (9)
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The entire history of HIV-1 is hidden in its ten thousand bases, where information regarding its evolutionary traversal through the human population can only be unlocked with fine-scale sequence analysis. Measurable footprints of mutation and recombination have imparted upon us a wealth of knowledge, from multiple chimpanzee-to-human transmissions to patterns

The entire history of HIV-1 is hidden in its ten thousand bases, where information regarding its evolutionary traversal through the human population can only be unlocked with fine-scale sequence analysis. Measurable footprints of mutation and recombination have imparted upon us a wealth of knowledge, from multiple chimpanzee-to-human transmissions to patterns of neutralizing antibody and drug resistance. Extracting maximum understanding from such diverse data can only be accomplished by analyzing the viral population from many angles. This body of work explores two primary aspects of HIV sequence evolution, point mutation and recombination, through cross-sectional (inter-individual) and longitudinal (intra-individual) investigations, respectively. Cross-sectional Analysis: The role of Haiti in the subtype B pandemic has been hotly debated for years; while there have been many studies, up to this point, no one has incorporated the well-known mechanism of retroviral recombination into their biological model. Prior to the use of recombination detection, multiple analyses produced trees where subtype B appears to have first entered Haiti, followed by a jump into the rest of the world. The results presented here contest the Haiti-first theory of the pandemic and instead suggest simultaneous entries of subtype B into Haiti and the rest of the world. Longitudinal Analysis: Potential N-linked glycosylation sites (PNGS) are the most evolutionarily dynamic component of one of the most evolutionarily dynamic proteins known to date. While the number of mutations associated with the increase or decrease of PNGS frequency over time is high, there are a set of relatively stable sites that persist within and between longitudinally sampled individuals. Here, I identify the most conserved stable PNGSs and suggest their potential roles in host-virus interplay. In addition, I have identified, for the first time, what may be a gp-120-based environmental preference for N-linked glycosylation sites.
ContributorsHepp, Crystal Marie, 1981- (Author) / Rosenberg, Michael S. (Thesis advisor) / Hedrick, Philip (Committee member) / Escalante, Ananias (Committee member) / Kumar, Sudhir (Committee member) / Arizona State University (Publisher)
Created2013
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Description
Vaccinia virus (VACV) is the current vaccine for the highly infectious smallpox disease. Since the eradication of smallpox, VACV has been developed extensively as a heterologous vaccine vector for several pathogens. However, due to the complications associated with this replication competent virus, the safety and efficacy of VACV vaccine vector

Vaccinia virus (VACV) is the current vaccine for the highly infectious smallpox disease. Since the eradication of smallpox, VACV has been developed extensively as a heterologous vaccine vector for several pathogens. However, due to the complications associated with this replication competent virus, the safety and efficacy of VACV vaccine vector has been reevaluated. To evaluate the safety and efficacy of VACV, we study the interactions between VACV and the host innate immune system, especially the type I interferon (IFN) signaling pathways. In this work, we evaluated the role of protein kinase R (PKR) and Adenosine Deaminase Acting on RNA 1(ADAR1), which are induced by IFN, in VACV infection. We found that PKR is necessary but is not sufficient to activate interferon regulatory factor 3 (IRF3) in the induction of type I IFN; and the activation of the stress-activated protein kinase/ c-Jun NH2-terminal kinase is required for the PKR-dependent activation of IRF3 during VACV infection. Even though PKR was found to have an antiviral effect in VACV, ADAR1 was found to have a pro-viral effect by destabilizing double stranded RNA (dsRNA), rescuing VACVΔE3L, VACV deleted of the virulence factor E3L, when provided in trans. With the lessons we learned from VACV and host cells interaction, we have developed and evaluated a safe replication-competent VACV vaccine vector for HIV. Our preliminary results indicate that our VACV vaccine vector can still induce the IFN pathway while maintaining the ability to replicate and to express the HIV antigen efficiently. This suggests that this VACV vector can be used as a safe and efficient vaccine vector for HIV.
ContributorsHuynh, Trung Phuoc (Author) / Jacobs, Bertram L (Thesis advisor) / Hogue, Brenda (Committee member) / Chang, Yung (Committee member) / Ugarova, Tatiana (Committee member) / Arizona State University (Publisher)
Created2013
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The transmembrane subunit (gp41) of the envelope glycoprotein of HIV-1 associates noncovalently with the surface subunit (gp120) and together they play essential roles in viral mucosal transmission and infection of target cells. The membrane proximal region (MPR, residues 649-683) of gp41 is highly conserved and contains epitopes of broadly neutralizing

The transmembrane subunit (gp41) of the envelope glycoprotein of HIV-1 associates noncovalently with the surface subunit (gp120) and together they play essential roles in viral mucosal transmission and infection of target cells. The membrane proximal region (MPR, residues 649-683) of gp41 is highly conserved and contains epitopes of broadly neutralizing antibodies. The transmembrane (TM) domain (residues 684-705) of gp41 not only anchors the envelope glycoprotein complex in the viral membrane but also dynamically affects the interactions of the MPR with the membrane. While high-resolution X-ray structures of some segments of the MPR were solved in the past, they represent the pre-fusion and post-fusion conformations, most of which could not react with the broadly neutralizing antibodies 2F5 and 4E10. Structural information on the TM domain of gp41 is scant and at low resolution.

This thesis describes the structural studies of MPR-TM (residues 649-705) of HIV-1 gp41 by X-ray crystallography. MPR-TM was fused with different fusion proteins to improve the membrane protein overexpression. The expression level of MPR-TM was improved by fusion to the C-terminus of the Mistic protein, yielding ∼1 mg of pure MPR-TM protein per liter cell culture. The fusion partner Mistic was removed for final crystallization. The isolated MPR-TM protein was biophysically characterized and is a monodisperse candidate for crystallization. However, no crystal with diffraction quality was obtained even after extensive crystallization screens. A novel construct was designed to overexpress MPR-TM as a maltose binding protein (MBP) fusion. About 60 mg of MBP/MPR-TM recombinant protein was obtained from 1 liter of cell culture. Crystals of MBP/MPR-TM recombinant protein could not be obtained when MBP and MPR-TM were separated by a 42 amino acid (aa)-long linker but were obtained after changing the linker to three alanine residues. The crystals diffracted to 2.5 Å after crystallization optimization. Further analysis of the diffraction data indicated that the crystals are twinned. The final structure demonstrated that MBP crystallized as a dimer of trimers, but the electron density did not extend beyond the linker region. We determined by SDS-PAGE and MALDI-TOF MS that the crystals contained MBP only. The MPR-TM of gp41 might be cleaved during or after the process of crystallization. Comparison of the MBP trimer reported here with published trimeric MBP fusion structures indicated that MBP might form such a trimeric conformation under the effect of MPR-TM.
ContributorsGong, Zhen (Author) / Fromme, Petra (Thesis advisor) / Mor, Tsafrir (Thesis advisor) / Ros, Alexandra (Committee member) / Redding, Kevin (Committee member) / Arizona State University (Publisher)
Created2014
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Luc Montagnier studied viruses, the immune system, and cancer in France during the second half of the twentieth century. In his early career, Montagnier studied how cancer-causing viruses replicate and infect host cells. He received the Nobel Prize in Physiology or Medicine in 2008 for his team’s discovery that a

Luc Montagnier studied viruses, the immune system, and cancer in France during the second half of the twentieth century. In his early career, Montagnier studied how cancer-causing viruses replicate and infect host cells. He received the Nobel Prize in Physiology or Medicine in 2008 for his team’s discovery that a retrovirus, human immunodeficiency virus, or HIV, was the cause of acquired immunodeficiency syndrome, or AIDS. AIDS is a chronic condition that results from HIV infection and damages the immune system. People who have AIDS typically experience increased vulnerability to a variety of diseases. Before Montagnier’s research on the virus, the exact cause of AIDS remained unknown to researchers and healthcare professionals. Beyond discovering HIV as the cause of AIDS, Montagnier’s work advanced a general understanding of how viral infection affects the immune system of the host organism.

Created2022-11-03
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To address the international Human Immunodeficiency Virus epidemic, the World Health Organization, or WHO, developed three drug treatment regimens between 2010 and 2012 specifically for HIV-positive pregnant women and their infants. WHO developed the regimens, calling them Option A, Option B, and Option B+, to reduce or prevent mother-to-child, abbreviated

To address the international Human Immunodeficiency Virus epidemic, the World Health Organization, or WHO, developed three drug treatment regimens between 2010 and 2012 specifically for HIV-positive pregnant women and their infants. WHO developed the regimens, calling them Option A, Option B, and Option B+, to reduce or prevent mother-to-child, abbreviated MTC, transmission of HIV. Each option comprises of different types and schedules of antiretroviral medications. As of 2018, WHO reported that in Africa alone about 1,200,000 pregnant women were living with untreated HIV. Those women have up to a forty-five percent chance of transmitting HIV to their offspring if they do not receive treatment. Option B+ has decreased the overall maternal mortality rates in many low- and middle-income countries, and numerous studies have supported the notion that it is the most effective of the three regimens for preventing MTC transmission of HIV.

Created2021-03-01
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In 2018, researchers Elie Nkwabong, Romuald Meboulou Nguel, Nelly Kamgaing, and Anne Sylvie Keddi Jippe published, “Knowledge, Attitudes, and Practices of Health Personnel of Maternities in the Prevention of Mother-To-Child Transmission of HIV in a sub-Saharan African Region with High Transmission Rate: Some Solutions Proposed,” in BMC Pregnancy and Childbirth.

In 2018, researchers Elie Nkwabong, Romuald Meboulou Nguel, Nelly Kamgaing, and Anne Sylvie Keddi Jippe published, “Knowledge, Attitudes, and Practices of Health Personnel of Maternities in the Prevention of Mother-To-Child Transmission of HIV in a sub-Saharan African Region with High Transmission Rate: Some Solutions Proposed,” in BMC Pregnancy and Childbirth. In their article, hereafter “Knowledge, Attitudes, and Practices,” the authors state the aim of their study was to establish the knowledge, attitudes, and practices held by health professionals who worked in numerous maternal departments throughout Cameroon. They claimed that effective knowledge, attitudes, and practices would likely reduce mother-to-child, hereafter MTC, transmission of HIV. After finding a deficit in the knowledge, attitudes, and practices among a subset of health professionals, the authors recommended increased training, funding, and supervision to reduce MTC transmission of HIV throughout Cameroon.

Created2021-04-06
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In 2011, Inga Kristen, Julius Sewangi, Andrea Kunz, Festo Dugange, Judith Ziske, Brigitte Jordan-Harder, Gundel Harms, and Stefanie Theuring published the article, “Adherence to Combination Prophylaxis for Prevention of Mother-to-Child-Transmission of HIV in Tanzania,” in PLoS ONE. Hereafter, “Adherence to Combination Prophylaxis,” the article details the authors’ investigation into the

In 2011, Inga Kristen, Julius Sewangi, Andrea Kunz, Festo Dugange, Judith Ziske, Brigitte Jordan-Harder, Gundel Harms, and Stefanie Theuring published the article, “Adherence to Combination Prophylaxis for Prevention of Mother-to-Child-Transmission of HIV in Tanzania,” in PLoS ONE. Hereafter, “Adherence to Combination Prophylaxis,” the article details the authors’ investigation into the efficacy of a medication regimen called combination prophylaxis to prevent mother-to-child, or MTC, transmission of Human Immunodeficiency Virus, or HIV, before, during, and after delivery. They included pregnant women who had HIV, in Kyela, Tanzania. However, through interviews and surveys, the authors found that many women had difficulty adhering to the regimen, which made the medication less effective. Kristen and colleagues suggest that healthcare professionals who treat HIV-positive pregnant women increase hospital resources and prescribe medication to those women early in the pregnancy to reduce MTC transmission of HIV.

Created2021-04-03
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Ian Hector Frazer studied the human immune system and vaccines in Brisbane, Australia, and helped invent and patent the scientific process and technology behind what later became the human papillomavirus, or HPV, vaccinations. According to the Centers for Disease Control and Prevention of the US, or CDC, HPV is the

Ian Hector Frazer studied the human immune system and vaccines in Brisbane, Australia, and helped invent and patent the scientific process and technology behind what later became the human papillomavirus, or HPV, vaccinations. According to the Centers for Disease Control and Prevention of the US, or CDC, HPV is the most common sexually transmitted infection, and can lead to genital warts, as well as cervical, head, mouth, and neck cancers. Frazer and virologist Jian Zhou conducted research in the 1990s to assess why women with HPV had higher rates of precancerous and cancerous cervical cells. Frazer’s research led the pharmaceutical company Merck to produce the Gardasil vaccination series, and GlaxoSmithKline to produce the Cervarix vaccination. Frazer’s research contributed to the development of HPV vaccinations that have been successful in reducing up to seventy percent of cervical cancer cases in women.

Created2020-09-02
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L'Institut Pasteur (The Pasteur Institute) is a non-profit private research institution founded by Louis Pasteur on 4 June 1887 in Paris, France. The Institute's research focuses on the study of infectious diseases, micro-organisms, viruses, and vaccines. As of 2014, ten scientists have received Nobel Prizes in physiology or medicine

L'Institut Pasteur (The Pasteur Institute) is a non-profit private research institution founded by Louis Pasteur on 4 June 1887 in Paris, France. The Institute's research focuses on the study of infectious diseases, micro-organisms, viruses, and vaccines. As of 2014, ten scientists have received Nobel Prizes in physiology or medicine for the research they have done at the Pasteur Institute. Contrary to the way genetics was studied in US research universities during the mid-twentieth century, the genetic research conducted at the Pasteur Institute at the same time did not rest on a conceptual separation between embryology and evolution. According to historian Michel Morange from the Ecole Normale Superieure in Paris, France, this difference enabled Pasteurian scientists to develop the concepts of regulatory genes and of developmental genes.

Created2014-08-19