The Human Immunodeficiency Virus -1 (HIV-1) has been the source of substantial human misery since it was first discovered in the early 1980s. Despite remarkable progress that has been made towards understanding HIV- 1, there is no cure, no vaccine and life-prolonging therapies are beyond the reach of millions in need. Our research sought to both gain insight into potential therapeutic targets as well as the preclinical testing of drug candidates. We demonstrate that a RhoA derived peptide is an effective inhibitor of HIV-1 entry. Although this peptide inhibits HIV-1 due to its poly-anionic nature, it nevertheless demonstrates that endogenous host proteins may be repurposed for novel therapeutic uses. We also characterized the mechanism and effectiveness of Basant, a polyherbal topical microbicide candidate for the prevention of HIV-1 transmission. Our data demonstrate that it inhibits the entry of both CCR5 and CXCR4 tropic HIV-1 at non-toxic concentrations. Finally, data is presented on the characterization of a novel HIV-1 protein expressed from an alternative reading frame of the HIV-1 polymerase gene. We demonstrate that this protein is localized to the nucleolus and is likely expressed from a novel HIV-1 transcript. This work lays the foundation for further studies to target this protein for drug development. / Graduation date: 2011 / Access restricted to the OSU Community at author's request from May 9, 2011 - May 9, 2012

As a defense against viral infection, plants are thought to use RNA-induced silencing complexes (RISCs) to target and cleave viral RNA. To counteract this, some viruses have evolved proteins to inhibit RISC-mediated activity, thus ensuring continued virulence. This research focused on the study and analysis of the anti-viral RNAi response to various viruses in plants to gain an understanding of how the plant defense operates on the molecular and biochemical levels. Nicotiana benthamiana plants were infected with Tomato bushy stunt virus (TBSV) and Tobacco rattle virus (TRV). These plants were subjected to column chromatography methods, and fractions contained a virus-specific ribonuclease activity, co-eluting with small interfering RNAs (siRNA), that was shown to be sensitive to inhibition with EDTA and enhanced by the addition of divalent metal cations. This ribonuclease activity co-purified with proteins that contained a domain from the hallmark RISC protein Argonaute family. To further study host responses to viral infection, monocots were infected with Panicum mosaic virus (PMV) and satellite panicum mosaic virus (SPMV) and also were subjected to column chromatography following infection. Preliminary studies show that fractions contained ribonuclease activity as well as siRNAs and proteins containing an Argonaute domain. Additionally, silencing suppressors have been directly implicated in interfering with RNAi pathways in plants. Studies involving Agrobacterium- and virus-vectored cDNA to express green fluorescent protein (GFP) were used to establish that cointroduced suppressors of RNAi can extend the production of a foreign protein for enhancement of biotechnological applications. It was found that the hordeivirus protein ?b contributes to enhancement of expression for the foreign protein GFP early in the infection, while the potyvirus protein HcPro and tombusvirus protein P19 enhance and extend protein production later in the infection.

Influenza epidemics have always been a constant public health threat to human populations. Recent societal developments and demographics changes have put us at increased risk of a widespread and potentially deadly influenza epidemic. Antiviral prophylaxis may provide an important epidemic intervention measure especially against influenza epidemic caused by novel influenza viruses where there will be no effective epidemic-specific vaccines available at the initial phase of the epidemic. Antiviral prophylaxis is listed as a fundamental component of the Hong Kong Preparedness Plan for Influenza Pandemics, however the rationale of such plan is not supported by public presentation of scientific evidence and no details of the actual antiviral prophylaxis plan are provided. With a majority of its stockpile set to expire in the very near future, we would like to know if antiviral prophylaxis is an effective intervention strategy against influenza epidemic and should antiviral stockpiling be continued. We identified relevant studies and reviewed the effectiveness of antiviral prophylaxis in preventing influenza infections at the individual, household and population level. We found that prophylactic treatment with Oseltamivir or Zanamivir are both effective in preventing influenza infections at the individual and household level. Both antivirals are well tolerated and neither is associated with major adverse events. Antiviral prophylaxis is effective in mitigating the public health impact of an influenza epidemic such as number of clinical influenza infections, hospitalization and deaths. However, antiviral prophylaxis alone may not be sufficient to contain or avert an influenza epidemic or delay the epidemic progress long enough for public health resources such as epidemic-specific vaccines to be acquired. In addition, the emergence of antiviral resistance and various logistics constraints will hamper the effectiveness of antiviral prophylaxis in containing influenza epidemics. We suggest the use of antiviral prophylaxis as the key intervention to mitigate influenza epidemics, however, with special considerations taken into hedging antiviral resistance and fulfilling the logistics requirements in order to make antiviral prophylaxis effective. In addition, we recommend public health authorities to take a multi-factorial approach in tackling highly transmissible influenza epidemics by incorporating other non-pharmaceutical interventions such as quarantine, school closures and boarder restrictions into the their antiviral prophylaxis-based containment plan. / published_or_final_version / Public Health / Master / Master of Public Health

No description available.

No description available.

In light of the remarkable antiviral activity of acyclic nucleoside analogues such as that of BIOLF-62 against the herpes viruses, a number of products in which heterocyclic bases were coupled to the active acyclic sugar moiety were prepared and submitted for biological testing. / Various dimethoxytritylated and t -butyldimethylsilylated derivatives of arabinoadenosine were prepared and fully characterised by $ sp1$H and $ sp{13}$C NMR spectroscopy. $ sp{29}$Si INEPT as well as $ sp{29}$Si-$ sp1{ rm H}$ correlated NMR were used to study various t -butyldimethylsilyl and triisopropylsilyl substituted ribonucleosides. / In an effort aimed at the development of new and better nucleoside protecting functions, the 2,4-dinitrobenzenesulfenyl group which is stable to both acidic and basic conditions, was used for $5 sp prime$-hydroxyl protection of ribonucleosides and its compatibility with the phosphodichoridite nucleoside coupling procedure was investigated. The nitrobenzenesulfenyl group was used in conjunction with the dimethoxytrityl group for $2 sp prime$-hydroxyl protection in the synthesis of a UpU dimer. The latter was fully characterised by enzymatic degradation and HPLC analysis of the products.

Thesis (M. P. H.)--University of Hong Kong, 2007.

Thesis (M.Sc.)--York University, 2006. Graduate Programme in Biology. / Typescript. Includes bibliographical references (leaves 95-103). Also available on the Internet. MODE OF ACCESS via web browser by entering the following URL: http://gateway.proquest.com/openurl?url_ver=Z39.88-2004&res_dat=xri:pqdiss&rft_val_fmt=info:ofi/fmt:kev:mtx:dissertation&rft_dat=xri:pqdiss:MR19730

Thesis (M. P. H.)--University of Hong Kong, 2007. / Also available in print.

Diss. (sammanfattning) Stockholm : Karol. inst., 2001. / Härtill 6 uppsatser.