William McD. Hammon, MD, PhD Chairman, Department of Epidemiology and Microbiology 1949-1970

Significant Accomplishments of the IDM Faculty
During the Last 50 Years

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The 1990s

• Drs. Rinaldo, Gupta, and colleagues showed that high cytotoxic T lymphocyte immune responses and low amounts of virus in the blood are directly related to non-progression of HIV infection. The discovery of this protective mechanism yielded a better understanding of how HIV functions and ways to control the disease.
• Dr. Mellors and colleagues in the Pitt Men’s Study were the first to show that the level of virus in blood, known as the viral load, is the best predictor of disease development. This work has provided physicians around the world with a simple measure for prognosis of HIV infection, and is now the main basis for assessment of HIV therapy.
• Dr. Mellors and colleagues at the PTEU as part of a nationwide clinical trial demonstrated that therapy with combinations of anti-HIV protease inhibitors and reverse transcriptase inhibitors significantly reduces viral load in blood and decreases morbidity and mortality. This study was a monumental advance toward a cure for AIDS.
• Dr. Rowe was the first to discover that the LMP2A gene of Epstein Barr virus (EBV) is responsible for latency of EBV in blood cells. This has revealed new facets of genetic control of EBV latency that have important implications for therapy and prevention of EBV-related diseases.
• Dr. Gupta, together with Pitt Men’s Study and PTEU colleagues, were the first to show high levels of virus in semen at all stages of HIV infection, thus providing evidence that men can potentially transmit HIV at any time during infection. Therapy with potent antiviral drugs significantly reduced the viral load in semen, implying that such therapy can lower transmission of HIV.
• Dr. Rinaldo, with his graduate student, John Ferbas, Dr. Xiao-Li Huang, and Dr. Zheng Fan, showed that dendritic cells, the most potent antigen presenting cells in the body, are the main producers of interferon alpha and can stimulate anti-HIV T cell responses. This provides a new approach to restore the immune system in AIDS patients.
• Drs. Kingsley, Gupta, and Rinaldo, in collaborations led by Columbia University investigators, showed that a new herpesvirus, Kaposi’s sarcoma associated herpesvirus, infects homosexual men and may be the etiologic agent of Kaposi’s sarcoma.
• Dr. Rinaldo as part of MACS collaborations showed persons with certain HLA and chemokine receptor genetic types were either more or less susceptible to HIV-1 disease progression. This is important to our understanding of why people develop AIDS at different rates.
• Dr. Silvestre showed that young men were still becoming infected with HIV at an alarming rate in the early 1990s. His finding that 7% of these men were already infected by the age of 22 was verified in a number of later studies in other areas of the country.
• Dr. Silvestre, Mr. Matthew Moyer, and Dr. Rinaldo organized a community educational program called the Youth Empowerment Project to reach young people at risk of HIV infection in Pittsburgh.
• Dr. Silvestre headed a team to develop annual HIV prevention plans for the Commonwealth (excluding Philadelphia). The team also developed demonstration projects, an Internet page (stophiv.com), and a project to mentor youth through youth round tables. These gather data for planning and community-led programs in eight Pennsylvania cities, particularly focusing on racial, ethnic, and sexual minority populations.
• Dr. Tung was one of the first to develop the SIV model for gene therapy of AIDS. This area is being actively investigated as a therapeutic approach for AIDS patients.
• Dr. Rinaldo and colleagues in the PTEU showed that potent antiretroviral therapy greatly restores T cell immunity to HIV and other microbial agents, but that this enhancement is incomplete. This has important implication for the long-term efficacy of these antiviral drug therapies.
• Dr. Rowe developed a quantitative assay to measure the level of EBV in blood that is now being used across the nation to monitor transplant recipients for EBV infection and lymphoma development.

The 1980s

• Drs. Pasculle, Rinaldo, and Myerowitz discovered the "Pittsburgh Pneumonia Agent". This proved to be a new species of the Legionella bacterium, later termed Legionella micdadei, that caused pneumonia in normal and immunocompromised hosts.
• Dr. Yu and his graduate students, Janet Stout and Jeff Zuravleff, showed that Legionella pneumophila was ubiquitious in the water supply of a hospital with endemic Legionnaires' disease. This was the basis for further studies showing that heating or chlorinating of water sources could decrease the spread of the bacteria.
• Drs. Ho, Armstrong, Breinig, and colleagues showed that development of lymphoma in organ transplant recipients is caused by Epstein Barr virus, a herpesvirus transmitted through the donated organ.
• Dr. Rinaldo established the Pitt Men’s Study of the national Multicenter AIDS Cohort Study (MACS), the largest and most extensive epidemiologic study of HIV/AIDS in the world. The MACS has produced over 500 scientific publications. During the last 15 years the Pitt Men’s Study has secured over 40 million dollars of extramural funding, and has been the foundation for the subsequent growth and prominence of HIV-related studies in the GSPH and the University of Pittsburgh.
• Dr. Ho established the first clinical trials center for HIV in Pennsylvania (Pittsburgh Treatment Evaluation Unit; [PTEU]). The PTEU, now led by Dr. Mellors, is still the most comprehensive clinical center of HIV/AIDS treatment in Western Pennsylvania.
• Dr. Kingsley was the first to establish clearly that anal receptive intercourse is the major risk factor for transmission of HIV among homosexual men.
• Drs. Koros, Weinbaum, and Atchison found lymphocyte antigens expressed on certain forms of lung cancer. The use of monoclonal antibodies to target therapy for these forms of cancer is offering more specific treatments than conventional chemotherapy or radiation.
• Drs. Frank, Ho, and Silvestre organized the Pennsylvania AIDS Education and Training Center to educate health care providers throughout Pennsylvania about HIV and AIDS.

The 1970s

• Dr. Ho and colleagues produced elegant work on the regulation of interferon in cells and ways to enhance it.
• Drs. Ho, Armstrong, and colleagues made one of the most important discoveries on the epidemiology of cytomegalovirus (CMV) infection by showing that CMV is transmitted to transplant recipients by the transplanted organ. This formed the basis for rigorous testing of transplant donors for CMV, and current drug therapy protocols following transplantation.
• Dr. Rinaldo and colleagues showed that CMV is highly immunosuppressive, which subsequently served as one of the first indications of the profound immunosuppressive effects of AIDS.

The 1960s

• Dr. Ho and colleagues did pioneering work on the cellular production of interferon induced by bacteria and bacterial toxin, thus providing valuable information on the mechanisms of host immune response against bacterial infections.
• Drs. Atchison and Hammon discovered adeno-associated virus, which is now extensively used to deliver genes in therapy of many human diseases.

The 1950s

• Dr. Hammon did pioneering work on the prevention of polio in children by intravenous injection of gamma globulin. This study formed a basis for the subsequent development of the Salk polio vaccine at the University of Pittsburgh.
• Dr. Hammon was the first to recognize dengue hemorrhagic fever disease and discovered dengue virus, which was the causative agent.
• Dr. Ho was the first to demonstrate interferon production in cell culture, this being one of the first recognized "cytokines" which are now known to have numerous antiviral and cell regulatory functions.

The 1940s

• Dr. Hammon was the first to establish the mosquito as the major epidemic vector of the Western Equine encephalitis virus and thus coined the presently used term of this group of viruses as "arthropod-borne viruses (arboviruses)."