2nd International Conference on Retroviruses and Novel Drugs June 30- July 01, 2016 Cape Town, South Africa

Biography:

Abstract:

The J subgroup avian leukosis virus (ALV-J) infects domestic chicken, jungle fowl, and turkey and enters the host cell through a receptor encoded by tvj locus and identified as Na+/H+ exchanger 1 (NHE1). The resistance to ALV-J in a great majority of galliform species was explained by deletions or substitutions of the critical tryptophan 38 in the first extracellular loop of NHE1. Because several cases of ALV-J positivity have been reported in feral duck species recently in Asia, we studied the natural polymorphisms of NHE1 in wild ducks, geese, and other avaian species. In parallel, we examined the NHE1 polymorphism in domestic chicken breeds where we documented differences in their susceptibility to ALV-J in vitro. In a panel of chicken breeds assembled with the aim to cover the maximum variability encountered in domestic chickens, we found a completely uniform sequence of NHE1 extracellular loop 1 (ECL1) without any source of genetic variation for the selection of ALV-J-resistant poultry. In wild bird species, mostly galloanseriforms, we demonstrate polymorphic amino-acids and the prevalent absence of the critical tryptophan residue within ECL1. In several species, the W38 was detected and the susceptibility to ALV-J was confirmed by infection of primary cells in culture. Our results will be discussed as to the chance of ALV-J to be transmitted to new hosts and to establish tha natural reservoir of circulating virus with potential of further evolution.

Biography:

Anna Coussens obtained her PhD in Australia at the Queensland University of Technology, in Cellular and Molecular biology. After completing a postdoc at the National Institute of Medical Research in the UK, she moved to the University of Cape Town in 2012, to develp a research program in clinical TB-HIV immnology. She is a Senior Lecturer in the Division of Medical Microbiology, within the Institute of Infectious Disease and Molecular Medicine. She recently began her on research group focusing on host directed therapies and biomarkers of subclincal infection. She is currenly an executive committee member of the Global Young Academy.

Abstract:

Tuberculosis (TB) susceptibility is influenced by immunosuppression during Mycobacterium tuberculosis (Mtb) infection. Amongst the greatest risk factors for TB are HIV-1 infection and vitamin D deficiency. These risks factors are not mutually exclusive and exacerbate eachother. However, the phenotype of immunodeficiency induced by each is different, therefore their interrelationship on suceptiblity is complex. Co-infection with HIV is thought to increase susceptibility to TB via a number of mechanisms; primarily through dysfunctional and decreased CD4+ T cells and impaired T cell activation. However, the impact on innate immuity which may influce the primary response to Mtb is less clear. Vitamin D deficiency not only associates with TB risk, but it is greater in HIV-co-infected patients. The effects of vitamin D on the immune system are pleiotropic, being both anti-inflamamtory and anti-microbial. Consequently, the exact mechanisms by which vitamin D may help prevent and treat TB-HIV remain contentious. Evidence suggests that vitamin D may not only reduce risk of TB by increasing anti-mycobacterial immunity and reducing inflammation, but it may also reduce HIV replication and the associated effects on innate and adaptive immunity; thus concomitantly reducing the associated risk of HIV on TB. I will summarise our in vitro and ex vivo findings in various populations on the effect of vitamin D supplemention on the response of innate and adaptive immunity to HIV-Mtb infection, and demonstrate the effects of local inflammation on the cellular response to co-infection. Vitamin D may prove to be a cheap, effective, tool for preventing TB-HIV disease progression.

Biography:

Abstract:

The concurrent use of hormonal contraception and ARVs is likely to increase with the implementation of programs using ARVs to prevent HIV infection. However, little is known about the combinatorial effects of different ARVs and progestins used in hormonal contraception, both systemically and in the female genital tract. In this study we investigated the effects of the ARVs dapivirine (DPV) and tenofovir disproxil fumarate (TDF) alone and in combination with medroxyprogesterone acetate (MPA) on select immune function gene expression. Cervical TZM-bl cells were exposed to varying concentrations of DPV and TDF on their own, or in combination with 100 nM MPA or the glucocorticoid dexamethasone (DEX). Results show that upregulation of IL-8 mRNA in TZM-bl cells occurs at high concentrations (1, 10 uM) of TDF or DPV in a time-dependent manner. On their own, DEX or MPA also resulted in a pro-inflammatory IL-8 response, which is greatly potentiated upon co-stimulation with 1 µM DPV, while co-stimulation with 1 µM TDF resulted in an additive IL-8 pro-inflammatory response. mRNA levels of the anti-inflammatory gene, GILZ, which is transactivated by DEX or MPA alone, remained unchanged by up to 10 µM of either ARV, while the ARVs alone had no effect on GILZ mRNA levels. Only high concentrations of DPV but not TDF reduced the cell viability. Results from this study suggest that DPV or TDF have differential effects on select immune function genes and may exert cytotoxic effects directly on cervical epithelial cells, which may be potentiated by MPA. These results may aid in the choice of ARV for combination with progestins, to protect against HIV infection and unwanted pregnancies with minimal side effects.

Biography:

Phetole Walter Mahasha, has completed his PhD at the age of 38 years from the University of Pretoria, South Africa and Postdoctoral studies from the University of Virginia, School of Medicine, Division for infectious Diseases and International Health and the Center for Public Health Genomics and the University of Venda, AIDS Virus Research Programme and the NICD in South Africa. He is a Senior Lecturer, in the Department of Pre-Clinical Sciences (Medical Biochemistry) at the University of Limpopo. He has published more than 5 papers in reputed journals and has been serving as an editorial board member of repute.

Abstract:

Background: Due to its continuous exposure to food antigens and microbes, the gastrointestinal tract (GIT) is in a constant state of low level immune activation and contains an abundance of activated CCR5+CD4+ T lymphocytes, the primary target HIV-1. As a result, the GIT is a site of intense viral replication and severe CD4+ T cell depletion, a process that begins during primary HIV-1 infection and continues at a reduced rate during chronic infection in association with increased production of pro-inflammatory cytokines, a breakdown in the epithelial barrier, microbial translocation, systemic immune activation and the continued recruitment and infection of new target cells. AntiRetroviral Therapy (ART) is only partially effective in reversing these pathogenic changes. Despite the importance of the GIT in HIV-1 pathogenesis, and as a reservoir of persistent virus during ART, little is known about the diversity of HIV-1 in the GIT, or how different tissues in the GIT respond to ART. Objectives: Primary objectives of this thesis were to: 1) characterize the diversity of HIV-1 RNA variants in different parts of the GIT 2) determine whether there is compartmentalized evolution of HIV-1 RNA variants in the GIT and whether these variants are likely to have different biological properties. Methods: A prospective study of the duodenum, jejunum, ileum and colon of African AIDS patients with chronic diarrhea and/or weight loss, sampled before and during 6 months of ART. RNA extracted from gut biopsies was reverse transcribed and PCR amplified. Env and gag PCR fragments were cloned, sequenced and subjected to extensive phylogenetic analysis; pol PCR fragments were analyzed for drug resistance. Results: Viral diversity varied in different regions of the GIT with env HIV-1 RNA variants being significantly more diverse than gag variants. Gag HIV-1 RNA variants were widely dispersed among all tissue compartments. Some env variants formed tight monophyletic clusters of closely related viral quasispecies, especially in the colon, a finding that is suggestive of compartmentalized viral replication and adaptive evolution. Conclusions: These results advance our understanding of the GIT as a host-pathogen interface by providing new insights into the diversity, evolution and dissemination of HIV-1 variants in the GIT. Strategies aimed at decreasing immune activation, especially in the small intestine, may be highly beneficial in enhancing the therapeutic efficacy of ART.

Biography:

Professor Adeleye completed his PhD in 1990 from University of Ibadan, Nigeria and has been lecturing in Universities in Nigeria. He is currently the Head of Department of Microbiology, University of Lagos. He has published more than 50 papers in reputed journals and has been serving as an editorial board member of repute in a few journals.

Abstract:

Influenza A virus infections are of medical concern because of high mutation of their genes, viral transmission and increased resistance to available drugs. Actinomycetes have been recognized over decades for their ability to produce bioactive metabolites of therapeutic importance. The search for this group of bacteria have concentrated on the terrestrial environment and marine environment have been overlooked.It is therefore imperative to screenunder-explored environments such as Lagos Lagoon, for actinomycetes with ability to produce novel antiviral drugs that will help alleviate drug resistance. Actinomycetes were isolated from sediment samples from different sites of the Lagos Lagoon, by spread plate method using starch casein, Kuster’s, Gauze 1 and 2, marine and actinomycete isolation agar. Plates were incubated at 29 ^oC for 1 to 5weeks. Identification of the isolates was done using API kits and through amplification of 16S r RNA gene and sequencing using actinobacterial-specific primers. Extraction of secondary metabolites was carried out using equal volume ethyl acetate (1:1). Antiviral activity of the crude extracts on X-31 (H3N2) Influenza virus cultivated in MDCK-2 cells using 12-well plates, were also determined using plaque reduction assay. Cells were grown at 370C, in 12-well plates for 2 days. Streptomyces albusULK2 and Streptomyces avermitilisULK3 showed significant antiviral activity with extracts from the strain Streptomyces albusULK2 having activity at concentration as low as 0.5mg/ml. This study revealed for the first time, actinomycetes isolated from Lagos lagoon sediments having antiviral activities. Actinomycetes from underexplored Lagos lagoon could be potential source of novel bioactive compounds of therapeutic values.

Biography:

Brian Flepisi has completed his PhD in Pharnacology at the University of Stellenbosch. However, he is currently employed as a lecturer at the University of the Western Cape. His research interest is on HIV associated cancer.

Abstract:

It is evident that altered immune mechanisms play a critical role in the pathogenesis of Non Hodgkin lymphoma (NHL) [De Roos et al., 2012; Mellgren et al., 2012]. HIV infection is associated with a state of excessive T-cell activation [Cao et al., 2009], which has been associated with increased T-cell turnover and lymph node fibrosis [Haas et al., 2011]. The current study aimed to determine the serum levels of circulating B-cell activation markers, the expression of T-cell activation and regulatory markers in HIV positive NHL patients. The serum levels of circulating soluble sCD20, sCD23, sCD27, sCD30 and sCD44 cells were determined by enzyme linked immunosorbent assay (ELISA). Biomarkers of T-cell activation and regulation were determined by flow cytometry in 141 subjects that were divided into 5 groups: naive HIV+; cART treated HIV+; HIV negative NHL; HIV+ NHL and healthy controls. HIV+ NHL patients had significantly high serum levels of sCD20, sCD23, sCD30 and sCD44 as compared to NHL, while all 5 biomarkers including sCD27 were significantly elevated in HIV+ NHL when compared with cART treated HIV+ patients. HIV+NHL patients had higher CD8+CD38 and lower FoxP3 expression than NHL and cART treated HIV+ patients. B-cell activation is increased in HIV+NHL as evidenced by increased B-cell activation markers, and is associated with suppressed T-cell regulation and increased T-cell activation.

Biography:

Abstract:

Background: Studies of Antiretroviral Therapy program in Africa have shown high incidence rate of opportunistic infections in both Antiretroviral Therapy receiving and Pre ART Human Immunodeficiency Virus infected patients. However, incidence of opportunistic infections and factors that contribute for development of it were poorly described in Ethiopia especially in the study area. Objective: To determine the effect of HAART on incidence rate of opportunistic infections among HIV-positive adults in Public Health facilities of Arba Minch town. Method: Retrospective cohort study was used and the required sample size was 464. Study participants were selected randomly from the list of adult people living with HIV attending the public health facilities for ART. Univariate analysis was used to describe patients’ baseline and follow up characteristics. Kaplan-Meier survival and log rank test were used to estimate survival and compare survival curves respectively. Cox proportional-hazard regression model was used to determine independent predictors of incidence of opportunistic infections. Result: A total of 464 patients (232 in each cohort) contribute for 898.12 person years of follow up. The incidence of opportunistic infections was 55.8 per 100 person year and 3.4 per 100 person year of follow up in pre ART and HAART cohorts respectively. Being on HAART decreased occurrence of opportunistic infections by 93%. In contrary being male, being widowed, substance use, rural residence and having baseline CD4 count of 350-499 cells/μl are independent predictors of increased risk of opportunistic infections. Conclusion: The incidence of opportunistic infection was higher in pre ART cohort. Male gender, being widowed, substance use, rural residence and having baseline CD4 count of 350-499 cells/μl were independent predictors of increased risk of opportunistic infections.

Biography:

Faheem Seedat is a 3rd year resident in the Department of Internal Medicine at University of Witwatersrand. He is also currently enrolled for his Masters in Medicine at the University of Witwatersrand were his research is looking at the field of renal disease in patients with HIV.

Abstract:

Objective: There is limited data describing acute kidney injury (AKI) in HIV-infected adult patients in resource-limited settings where increasingly, tenofovir (TDF), which is potentially nephrotoxic, is prescribed. We describe risk factors for, and prognosis of AKI in HIV-infected individuals receiving and naïve to TDF. Methods: This was a prospective case cohort study of hospitalized HIV-infected adults with AKI (as defined by the 2012 KDIGO Clinical Practice Guideline for AKI) stratified by TDF exposure. Adults (≥18 years) were recruited: clinical and biochemical data was collected at admission; their renal recovery, discharge or mortality was ascertained as an in-patient and, subsequently, to a scheduled 3-month follow-up. Results: Amongst this predominantly female (61%), almost exclusively black African cohort of 175 patients with AKI, 93 (53%) were TDF exposed; median age was 41 years (IQR 35-50). Median CD4 count and VL and creatinine at baseline was 116 cells/mm3 and 110159 copies/ml, respectively. A greater proportion of the TDF group had severe AKI on admission (61% v 43% p=0.014); however, both groups had similar rates of newly diagnosed tuberculosis (TB) (52%) and NSAID (32%) use. Intravenous fluid was the therapeutic mainstay; only 7 were dialyzed. Discharge median serum creatinine (SCr) was higher in the TDF group (p=0.032) and fewer in the TDF group recovered renal function after 3-months (p=0.043). 3-month mortality was 27% in both groups but 55% of deaths occurred in hospital. Those that died had a higher SCr and more severe AKI than survivors; TB was diagnosed in 33 (70%) of those who died. Conclusions: AKI was more severe and renal recovery slower in the TDF group; co-morbidities and prognosis were similar regardless of TDF exposure. Because TB is linked to higher mortality, TB co-infection in HIV-infected patients with AKI warrants more intensive monitoring. In all those with poor renal recovery, our data suggests that a lower threshold for dialysis is needed.