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SPECIAL POINTS OF INTEREST: FHS Centenary 2 students graduated with PhDs Carolyn Williamsons Inaugural lecture

VIROLOGY MATTERS
V O L U M E 3

SEPTEMBER

2012

INSIDE THIS EDITION


History Med- 1-3 ical virology PhD graduates MPH graduate MPH graduate Virology publications Workshops 5-7 6 5 4

Medical Virology during 100 years of FHS at UCT


The Medical faculty was officially established in 1912 when a building was opened for the departments of Anatomy and Physiology. The chair of Bacteriology was established in 1918. In 1947 the Departments of Pathology, Bacteriology and Chemical Pathology were restructured as a combined Department of Pathology, with Marinus van den Ende, a UCT graduate, as overall head. The reorganisation had a a virological emphasis and in 1948 the South African Council for Scientific and Industrial Research (CSIR) created the Virus Research Unit, the first in South Africa, under his directorship. Marinus was always aware of the central role of the basic sciences in medical research and recruited Dr Tom Mead, a chemist and Dr Alfie Polson, a physicist. Dr Polson joined the unit as a research officer in 1952 and was still in action in the department in the early 1970s - he was considered a genius, particularly in the separation of molecules of different sizes. Prof Alfred Polson and Dr Golda Selzer were some of the first researchers to grow the polio virus in tissue culture and describe its physical and antigenic properties. Dr Selzer also developed a mouse model to understand the development of paralytic polio and she was the first Golda Selzer person to grow the Rubella virus from an aborted foetus from a mother who had been infected with Rubella. This was a key link in understanding the genesis of congenital cardiac defects associated with children born from mothers infected with this virus.

Inaugral lec9 ture & seminar Visitors & Conferences Events & Congratulations 11-12 10

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Brief history of Medical Virology continued


Many papers were published from the CSIR/UCT Virus Research Unit, including work on bacteriophages, influenza virus, poliomyelitis, Rift Valley fever, rabies and blue tongue, plus physical and chemical studies on viruses and general methods of virus research
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Prof Arthur Kipps research interests began in 1948 when he assisted van den Ende and they isolated an unknown virus from bovine lumpy skin disease. He became acting head of bacteriology in 1954 when van den Ende became Dean. In 1957, on the death of van den Ende, Arthur Kipps became Wernher and Beit Professor of Bacteriology and the head of the CSIR/UCT Virus Research Unit which he headed for 21 years. He spearheaded the move from the CSIR and in 1969 it became the MRC/UCT Virus Research Unit . Prof Kipps research Arthur Kipps included bovine lumpy skin disease and blue tongue disease in sheep. During his time as director, there were 200 publications from the unit of which he was co-author for 40. In 1978 the Chair of Clinical Virology was established. The first incumbent was Prof John Moodie who held the position until 1996. Under his mentorship the diagnostic service provided for the south and west of the country was expanded. It was a collaboration between UCT, the South African Institute for Medical Research (SAIMR) and the province. Prof Moodie s interests included research on Hepatitis B and meningitis. Prof Moodies tenure coincided with the first reports of HIV and it was durJohn Moodie ing this time that HIV testing started in Clinical Virology. He was very involved in HIV education and produced the HIV newsletter of the Western Cape. Prof Keith Dumbell joined Clinical Virology in 1982 and is now an emeritus professor. He had researched the smallpox virus since 1947 and was part of the successful campaign in the 1960s and 70s to eliminate smallpox from the globe. In the process, he built up the world's largest private collection of smallpox strains which in the interests of safety, he had to relinquish. Whist at UCT he led the pox virus group in the molecular characterisation of poxviruses. With Lafras Steyn (Medical Microbiology) Prof Dumbell started the Plasmid Unit in 1985. Deo de Wit started PCR by manually moving tubes from one water bath to another, meticulously timing each incubation step. Lafras and Deo, together with Mr Gerner, the in house instrument maker, made a PCR machine of 3 water baths before PCR machines were commercially available. In 1988 Virology obtained its first computer which was kept in the dark room! All researchers became photographers as they had to make their own prints from negatives and they had to make their own slides for conferences. Letraset was used extensively.

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Brief history of Medical Virology continued


Linda Stannard was an expert electron microscopist who worked in virology at UCT for over 20 years. Linda produced a global resource on Virus Ultrastructure: http://web.uct.ac.za/depts/mmi/stannard/linda.html In 1996 on Prof Moodies retirement the Chair of Clinical Virology was frozen. Dr G Anthony Keen became acting head of Medical Virology under the Department of Medical Microbiology. Dr Keen was a clinical pathologist who trained at UCT and who worked in Virology at UCT for over 30 years. Besides his teaching, clinical and diagnostic commitments his research interests included work on rubella, Hepatitis B, cytomegalovirus and meningitis.

Tony Keen

In 2000 the diagnostic services supervised by Dr Jane Yates (until 2004) and Dr Diana Hardie were integrated into the new National Health Services (NHLS) . The diagnostic laboratory has expanded from a small lab to a major facility which provides a comprehensive service to Groote Schuur Hospital and Red Cross Childrens Hospital, and is the referral laboratory for the Western Cape province. It is one of two centres in the Western Cape where HIV viral load and PCR testing is done for the CCMT programme. From April 2011 to March 2012 the laboratory performed approximately 85 000 HIV viral loads and 10 000 HIV PCR tests. Anna-Lise Williamson joined Virology in 1987 as a medical natural scientist and became an associate professor in 1999 and full professor in 2004. She was acting HODivision from 2006-2009. Her research interests include HIV vaccines, HPV and poxviruses. She has headed the South Africa AIDS Vaccine Initiative (SAAVI) funded vaccine development team since 2000. This team of people has been responsi- Anna-Lise ble for the development of two vaccines that were tested in Phase 1 Williamson clinical trials in the USA and South Africa. Carolyn Williamson joined Clinical Virology in 2002 as Associate Professor and became a full Professor in 2009. Carolyn became acting head of Division in August 2009 and HODivision in April 2010. Carolyn was co-PI for the SAAVI vaccine development tproject and was instrumental in the HIV vaccine design that is now in clinical trial. Carolyn leads the HIV Diversity and Pathogenesis Group which is involved in elucidating properties of recently transmitted virus, and understanding HIV evolution in response to cellular and antibody immune pressure. This research informs the design and evaluation of HIV-1 Vaccines

Carolyn Williamson

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cide trial who became HIVinfected, despite using tenofovir gel, had significantLindi Masson ly elevated genital tract inThesis Title: Impact of sexflammation compared to ually transmitted infections those who did not seroconand inflammation in the fevert, providing important inmale genital tract and blood sight into the mechanism for on susceptibility to HIV-1 inbreak-through infections in fection and disease progresthis trial. Lindi's thesis fursion ther showed that women Supervisor: who had inflammation in Dr Jo-Ann Passmore. their genital tracts during the Co-Supervisor: early stages of HIV infection had higher viral load setProf Carolyn Williamson. points and lower CD4+ T cell Lindi counts 12 month postMasinfection. son (nee Lycias Zembe RobThesis Title: Investigating erts) cross-clade immune rewas sponses in HIV-infected indiLindi with Prof viduals: Implications for HIV born in Carolyn William- Adelaide vaccine development son (left) and Dr in the Supervisor: Jo-Ann PassEastern Dr Wendy Burgers Cape. Co-Supervisor: Lindi completed her underProf Carolyn graduate studies (BSc) in Williamson Microbiology and Genetics at Lycias Zembe UCT in 2003 followed by her has a BSc BSc (Hons) and MSc( Med) (Hons) in Bioin Pharmacology in 2004 chemistry and 2007. She has been from the studying towards her PhD in Lycias with Prof University Medical Virology since Carolyn William- of Zimba2008. Lindi's thesis examson (left) and Dr bwe and ined the pivotal role of inWendy Burgers MSc (Med) in flammation in the female Medical Virology from the genital tract in susceptibility University of Cape Town. to HIV infection and subse- He joined the Division of quent HIV disease progres- Medical Virology in the Desion. Her thesis shows that partment of Clinical Laboratory Sciences as an MSc women participating in the CAPRISA tenofovir microbi- student in 2005 and registered for a PhD in 2008.
VIROLOGY MATTERS

PhD Graduates

Lycias Zembes PhD thesis characterised HIV-specific T-cell immune responses to different HIV clades that form the basis of current candidate HIV vaccines in development. The genetic diversity of the virus across the globe is a major impediment to developing a vaccine, and whether a universal vaccine that would be effective against all the clades is possible, is unknown. Lycias investigated whether HIV-specific Tcells in HIV clade C infected individuals from South Africa can cross-recognise the four major HIV clades, namely clade A, B, C and D. Lycias found that crossreactivity occurs frequently, and clusters of commonly targeted regions cross-reactive across the four clades reside predominantly in conserved regions. However, the magnitude and breadth of responses are greater for the matched clade compared to mismatched clades, suggesting that there may be an advantage of using a vaccine matching the viruses circulating in a particular geographical region. He also investigated the effects of minor changes in T cell epitopes on the functional characteristics of HIV-specific T-cells recognizing epitope variants, and found that there are discordant effects on the quality of HIV-specific immunity. These data inform the testing of current candidate HIV vaccines in different regions and have important implications for vaccine development.

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MPH Graduate
Dr Marvin Hsiao graduated with an MPH in June. The title of Marvins thesis was Analysis of HIV early infant diagnosis and linkage to care in the Western Cape: A laboratory perspective. Marvins project was done in collaboration with Landon Myer and Kathryn Stinson from the Centre of Infectious Disease Epidemiology and Research (CIDER) of the UCT Department of Public Health. The work was to outline the successes and failures of our early infant diagnosis and treatment programme in the Western Cape over the last 6 years. The main finding was that although only 65% of infants with a positive PCR result went on to received ART, this figure improved from 54% in 2005 to 71% in 2010. The work highlighted that in addition to the quality of testing, virology laboratories should also focus

Recent Virology Publications


Valley-Omar Z, Sibeko S, Anderson J, Goodier S, Werner L, Arney L, Naranbhai V, Treurnicht F, Abrahams MR, Bandawe G, Swanstrom R, Karim QA, Karim SS, Williamson C. CAPRISA 004 Tenofovir Microbicide Trial: No impact of Tenofovir gel on the HIV transmission bottleneck. J Infect Dis. 2012 Jul;206(1):35-40 Alterations of the genital mucosal barrier may influence the number of viruses transmitted from a human immunodeficiency virus -infected source host to the newly infected individual. We used heteroduplex tracking assay and single-genome sequencing to investigate the effect of a tenofovir-based microbicide gel on the transmission bottleneck in women who seroconverted during the CAPRISA 004 microbicide trial. Mariba Lebeko Seventy -seven percent (17 of 22; 95% confidence interval [CI], 56%90%) of women in the tenofovir gel arm were infected with a single virus compared with 92% (13 of 14; 95% CI, 67%->99%) in the placebo arm (P = .37). Tenofovir gel had no discernable impact on the transmission bottleneck

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Roberts L, Liebenberg L, Barnabas S, Passmore JA. Vaginal microbicides to prevent human immunodeficiency virus infection in women: Perspectives on the female genital tract, sexual maturity and mucosal inflammation. Best Pract Res Clin Obstet Gynaecol. 2012 Aug;26 (4):441-9. Epub 2012 Mar 17. Topically applied vaginal microbicides to protect against human immunodeficiency (HIV) virus infection offer an important female-controlled prevention strategy. Microbicides have been in development for more than 2 decades, and have included various agents that disrupt cellular and microbial membranes (surfactants), restore the natural acidic protective pH of the vagina (acid buffers), and those that interfere with interactions between HIV envelope proteins and cellular receptors (anionic polymers). Although none of these candidate microbicides have shown significant protection against HIV in clinical trials, a topical gel, including the antiretroviral drug tenofovir (TFV) 1% was the first microbicide to be tested to show some protection against HIV infection. This review explores the effect of female genital tract biology and anatomy, mucosal inflammation, and age on the effectiveness of microbicides to prevent HIV infection.
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Williamson AL, Rybiki E, Shephard E, Gray G, Bekker LG, Downing K, Williamson C. South African HIV-1 vaccine candidates - the journey from the bench to clinical trials. S Afr Med J. 2012 Mar 2;102(6):452-5. Abstract Around 2.5 million people become infected with human immunodeficiency virus (HIV) each year. This extraordinary toll in human life and public health worldwide will only be reversed with effective prevention. Vaccination is regarded as the most effective way to prevent infectious disease. However, there are many challenges to overcome before a successful prophylactic HIV vaccine will be available. We are participating in a global effort to develop and test candidate HIV vaccines. Two candidate prophylactic HIV vaccines that were designed and developed at the University of Cape Town (UCT) entered phase 1 Mariba Lebeko clinical trials in the USA and South Africa in 2009, after a 9-year development period. In addition to the vaccines in clinical trial, there is a pipeline of candidate HIV-1 subtype C vaccines including virus-like particles, novel DNA vaccines, capripoxvirus and Bacillus CalmetteGurin (BCG)-vectored vaccines. This article describes the history of HIV vaccine research at UCT, and the partnerships that made the project possible

VIROLOGY MATTERS

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Mbulawa ZZ, Marais DJ, Johnson LF, Coetzee D, Williamson AL. Impact of human immunodeficiency virus on the natural history of human papillomavirus genital infection in South African men and women. J Infect Dis. 2012 Jul 1;206(1):15-27. BACKGROUND: This study investigated genital human papillomavirus (HPV) incidence and clearance in 278 human immunodeficiency virus (HIV)-seropositive (HIV-positive) women, 208 HIV-negative women, 161 HIV-positive men, and 325 HIV-negative men, followed at 6-month intervals for up to 24 months. METHODS: HPV types were determined by the Roche Reverse Linear Array HPV genotyping assay. RESULTS: The rate of new HPV detection at the cervix and penis were 33.83 events/1000 person-months (95% confidence interval [CI], 26.39-43.46) and 55.68 events/1000 person-months (95% CI, 43.5969.19), respectively. HIV infection was associated with increased risk of new HPV detection in women (relative risk [RR], 2.98; 95% CI, 2.07-4.29) and men (RR, 2.00; 95% CI, 1.49-2.69). The risk of new HPV detection increased in women (RR, 5.25; 95% CI, 3.52-7.81) and men (RR, 8.71; 95% CI, 6.19-12.24) when the sexual partner was infected with the same HPV type. The rate of clearing any HPV infection was 95.1 events/1000 person-months (95% CI, 83.3-108.1) in men and 66.9 events/1000 person-months (95% CI, 57.0-78.5) in women. HIV infection reduced the rate of HPV clearance in women (RR, 0.46; 95% CI, .34-.62) and men (RR, 0.71; 95% CI, .55-.93). CONCLUSIONS: HIV infection increases the risk of new HPV detection and decreases the rate of HPV clearance in both women and men

Mlisana K, Naicker N, Werner L, Roberts L, van Loggerenberg F, Baxter C, Passmore JA, Grobler AC, Sturm AW, Williamson C, Ronacher K, Walzl G, Abdool Karim SS. Symptomatic vaginal discharge is a poor predictor of sexually transmitted infections and genital tract inflammation in high-risk women in South Africa. J Infect Dis. 2012 Jul 1;206(1):6-14. BACKGROUND: Diagnosis and treatment of sexually transmitted infections (STIs) is a public health priority, particularly in regions where the incidence of human immunodeficiency virus (HIV) infection is high. In most developing countries, STIs are managed syndromically. We assessed the adequacy of syndromic diagnosis of STIs, compared with laboratory diagnosis of STIs, and evaluated the association between STI diagnosis and the risk of HIV acquisition in a cohort of high-risk women. METHODS: HIV-uninfected high-risk women (n = 242) were followed for 24 months. Symptoms of STIs were recorded, and laboratory diagnosis of common STI pathogens was conducted every 6 months. Forty-two cytokines were measured by Luminex in cervicovaginal lavage specimens at enrollment. Human immunodeficiency virus type 1 (HIV-1) infection was evaluated monthly. RESULTS: Only 12.3% of women (25 of 204) who had a laboratory-diagnosed, discharge-causing STI had clinically evident discharge. Vaginal discharge was thus a poor predictor of laboratory-diagnosed STIs (sensitivity, 12.3%; specificity, 93.8%). Cervicovaginal cytokine concentrations did not differ between women with asymptomatic STIs and those with symptomatic STIs and were elevated in women with asymptomatic STIs, compared with women with no STIs or bacterial vaginosis. Although laboratory-diagnosed STIs were associated with increased risk of HIV infection (hazard ratio, 3.3 [95% confidence interval, 1.5-7.2)], clinical symptoms were not. CONCLUSIONS: Syndromic STI diagnosis dependent on vaginal discharge was poorly predictive of laboratorydiagnosed STI. Laboratory-diagnosed STIs were associated with increased susceptibility to HIV acquisition, while vaginal discharge was not

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Workshops
Lindi Masson returned to the Institute for Tropical Medicine in Antwerp (Belgium) for three weeks in June as part of a collaboration with Family Health International. While in Antwerp, she continued to measure levels of genital inflammatory cytokines in cervical swab samples from women participating in the FEM-PrEP oral Truvada trial. The purpose of this study is to determine whether genital inflammation played a role in HIV acquisition in women who became infected despite using oral Truvada. Ramla Tanko received a Scholarship for her MSc studies from the CanadaAfrica Prevention Trials (CAPT) Network, funded by the government of Canada, which was renewed for 2012. The network brings together scientific researchers in Uganda, South Africa, Kenya and Canada, and aims to develop necessary resources to mount appropriate prevention and treatment studies in sub-Saharan Africa. The 5th annual meeting of CAPT was held in March this year in Entebbe, Uganda. The objectives of the meeting were to review progress and to make a network work plan to enhance the development of research, training and capacity building. Ramla was given the opportunity not only to present her progress report at the meeting but also interact with the CAPT team, mentors and other scholars. In addition, she attended a workshop on scientific abstract and manuscript writing. The meeting was rewarding because of the knowledge gained from different fields of study and feedback she obtained from the mentors. Overall, the trip was a great success! In June, some of us from Medical Virology participated in a Writers Workshop, which was a 3-day weekend away at the Montfleur Conference Centre in StelDuring the course of the workshop, there were a few short seminars, but most of the time was dedicated to providing quality within the small groups, which was incredibly useful for our small group, and implementing these recommendations and discussions to improve and finalise the articles. To keep up the momentum gained during the Writers Workshop, a monthly follow-up will take place until all articles have been submitted. We are hoping that we can organise such a retreat for our Division for 2013, as it was fun, the setting and the food were wonderful, we got to know each other better, and most importantly, made excellent progress on our manuscripts. We thank Gaelle Ramon, our wonderful co-ordinator from the Research Office. Representing

lenbosch, sponsored by UCTs Research Office. We joined 10 other participants from Human Genetics. The purpose of the retreat was to give researchers time-away to finalise research articles in a beautiful setting, with helpful input provided through a process of critical peer review. The process started four months before the workshop, where researchers who had an article that they were intending to write up and submit in the next few months, made a commitment to participate in the Workshop. Several helpful seminars on writing and reviewing manuscripts were organised jointly by the two Divisions in the period leading up to the workshop, and two weeks before the workshop manuscripts in their most final form were sent to the Research Office. Participants were divided into groups, and a complete set of papers was given to members of each group to allow each person to review the other manuscripts.

Medical Virology were a group headed by Wendy Burgers, and including Gerald Chege, Andreia Soares, Cobus Olivier and Marcel Tongo. Thanks to Fiona Baine for the photos

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Inaugural lecture
Prof Carolyn Williamson gave her inaugural lecture entitled HIV: Surviving under immense pressure on Wednesday 23 May 2012. Carolyn eloquently described her journey as an HIV researcher over the last 20 years. Carolyn described the challenges faced in the laboratory as well as the political tribulations. Carolyn described HIV as her true passion in life. She gave an overview of the work her group are doing looking at the HIV genome particularly in recently transmitted viruses and how this may help in the development of an effective vaccine against HIV. Carolyn said that vaccines will likely be the best defence against HIV. She spoke about the candidate vaccine that she is involved in that is in clinical trials both in South Africa and the USA; it is a DNA/MVA prime boost vaccine.

Seminar
Andile Nofemela, a PhD student in Prof Carolyn Williamsons group arranged a seminar entitled A closer look at HIV transmission: A better understanding of multiple factors involved and future intervention methods as part of his David and Elaine Potter PhD Fellowship. For his PhD Andile is attempting to characterise the biological features of transmitted HIV viruses and their impact on disease progression. Andile invited a selection of eminent scientists and doctors to present at the seminar; these included Prof Anna-Lise Williamson who gave an introduction to HIV, Dr Jo-Ann Passmore who spoke on a model of HIV transmission. Andile, Melissa-Rose Abrahams and Gama Bandawe all spoke on aspects of the Virology of HIV transmission whilst Dr Max Kroon spoke on a paediatricians perspective on PMTCT. Prof Linda-Gail Bekker spoke on HIV and ART and Prof Robin Wood spoke on HIV and TB co-infection. Finally Prof Clive Gray gave an overview of HIV vaccine development. The seminar was an excellent overview on HIV - well done Andile!

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VISITORS
Prof Bert Jacobs was a visiting Fulbright specialist from the Biodesign Institute at the Arizona State University. He is a poxvirus researcher but has a special interest in HIV/AIDS education in Africa and spends time doing this in Tanzania each year. He spent a month in the division and gave a couple of
Prof Jacobs with Prof Anna-Lise Williamson (left)

Dieter Mielke is a third year student at UCT, majoring in Biochemistry and Physiology, and his interests lie in HIV-associated immunology (at least for now!). He worked in the HIV Diversity and Pathogenesis lab for 6 weeks during the winter vacation. He hopes do his honours in Infectious Diseases and Immunology in the Faculty of Health Sciences next year. Whilst here, he has undertaken small projects for staff as well as become competent in making competent cells for the lab!

Dr Lyle McKinnon from the University of Toronto and Kenyan AIDS Control Project, University of Nairobi gave a presentation entitled Characterising HIV target cells in the female genital tract of high-risk female sex workers

Conferences attended
In June, Anna-Lise Williamson, Niki Douglas, Olivia Carulei and Kristy Offerman exchanged their winter woollies for the seemingly never-ending sunshine of Salamanca, Spain. It was in this small, historical city, at the University of Salamanca (founded in the 1200s), where they attended the XIX International Poxvirus, Asfarvirus and Iridovirus conference. It was a fantastic conference, and great fun (and intellect) was enjoyed by all.

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EVENTS

Science Centre

In May, the Burgers Lab had an exciting day filled with lots of fun at the Science Centre in Observatory. We took 15 children from Lawrence House (Woodstock), which provides shelter and care to orphaned foreign and refugee children, to learn about science in a fun way. The event started off with the kids and us exploring the various science activities and puzzles, followed by a planetarium session where we were taken into the future, and life on the moon. Then we had lunch together, followed by an awesome chemistry demonstration (with lots of smoke and explosions). All in all, both the kids and us had a fantastic time, and we recommend the Centre to everyone.

Our group had yet another fun filled day with the kids at the Lawrence House Orphanage in September, after our previous trip with them to the Science Centre. We planned a baking feast where the guys in the lab (with zero baking experience) led and demonstrated to the kids how to bake biscuits. The guys did an amazing job at it, without ever stopping to glance at the recipes that they so cleverly laid in front of them! We made chocolate and various shapes of vanilla biscuits and the kids especially enjoyed icing and decorating the biscuits. The women in the lab kept a good look-out for any potential disasters, which fortunately did not happen! The event was a great success, as well as the biscuits, which magically disappeared in a blink of an eye. -Narjis, Wendys lab.

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CONGRATULATIONS!
Narjis Thawer obtained a DST fellowship for the 2012 South African Women in Science Awards by the Department of Science and Technology. The winners were announced in an award ceremony in Pretoria on the 24th August as part of the Departments celebration of National Womens Month

EVENTS

Mandela Day 18 July

Members of Virology (& Prof Jacobs) knitting squares or being supportive!

CONGRATULATIONS!
Carolyn Williamson and Tim Tucker got engaged whilst off-roading on their motor bikes in Angola in July. Photo taken at Kalundula Falls.

HIV Diversity Group

Katrina Downing again took part in the

Skukuza Marathon
The HIV Diversity Group went for tea at Rhodes Memorial to say farewell to Sarah Goodier
VIROLOGY MATTERS

Compiled and edited by Debbie Stewart (Debbie.stewart@uct.ac.za)

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