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Vanessa Pirrone

Vanessa Pirrone, PhD

Assistant Professor

Department: Microbiology & Immunology


  • PhD - Drexel University College of Medicine (2009)

Dr. Pirrone is an assistant professor in the Department of Microbiology & Immunology at Drexel University College of Medicine.

Research Overview

Research interests: Impact of age and HIV/HCV coinfection on HIV-1 replication, pathogenesis, and immune activation profiles.

Research Interests

Impact of age and HIV/HCV coinfection on HIV-1 replication, pathogenesis, and immune activation profiles


Aging is a complicated process involving several intrinsic and extrinsic factors intricately linked together, including different systems of the human body. Common aging-related chronic conditions include diabetes, lipidemia, cardiovascular disease, immune dysregulation, changes in bone strength and density, and neurologic impairment, including dementia syndromes such as Alzheimer’s disease (AD) and vascular dementia. These diseases are progressive and often are treatable but not curable.

Often these diseases coexist within the aging population. Prevalence of these diseases is increased among HIV-1-infected patients and current research suggests that this may be the result of premature aging associated with HIV-1 infection. Immunosenescence typically occurs in individuals greater than 70 years old. It is a general term used to describe an age-related decline in immune competence marked by alterations in the overall function of the immune system.

Immunosenescence is characterized by an increase in the number of terminally differentiated effector memory CD8+ T cells that are generally characterized by the inability to proliferate, the absence of CD28 expression, shortened telomeres, loss of telomerase activity, and enhanced secretion of inflammatory cytokines. The number of naïve CD8+ T cells also tends to decrease. In addition, the CD4+/CD8+ T cell ratio decreases, overall T cell activation increases, T cell proliferation and thymic involution are reduced, and levels of many inflammatory mediators increase. Immunosenescent phenotypes are generally accelerated by the presence of chronic infections, with cytomegalovirus implicated most often in aging. With HAART therapy resulting in a chronic type of HIV-1 infection, in which patients with well-controlled disease potentially live several decades, immunosenescence is occurring in patients with controlled disease as well as in those with uncontrolled disease. The immunosenescence observed appears premature, occurring in younger HIV-1-infected patients than what occurs in the general population. The phenotype is similar to that observed in older, noninfected people. Studies suggest that premature aging phenotypes in both the CD8+ and CD4+ T cell compartments predict faster clinical disease progression. HIV-1-associated immunosenescence may thus contribute to long-term continued immunodeficiency as well as to premature aging-associated diseases in infected patients.

Current research in the laboratory is investigating the potential that viral and host genetic factors alter susceptibility to accelerated HIV-associated aging events and negatively impact neurocognitive outcomes. This work will draw a molecular portrayal of aging of HIV+ patients utilizing unique longitudinal peripheral blood samples in conjunction with a comprehensive neurocognitive protocol from the DREXELMED HIV/AIDS Genetic Analysis Cohort divided into two groups: adult (age 30-45) and aged (age 50-65) as well as samples from the National NeuroAIDS Tissue Consortium (NNTC), derived from brain tissue in the absence or presence of minor or major neurocognitive impairment (NCI). This study utilizes molecular and systems biology approaches along with detailed immunological assessments to generate an overall picture of important pathways in HIV-1 pathogenesis and to determine how age affects these pathways, particularly those relevant to viral transcription and immune activation.

A second line of research in our laboratory focuses on HIV-1 and hepatitis C virus (HCV) coinfection in an aging population. A large number of HIV-1-infected individuals are coinfected with other viral and nonviral pathogens, including hepatitis C virus (HCV), which alone currently infects approximately 170 million individuals worldwide. Both HIV-1 and HCV share similar modes of transmission, and as such approximately 30% of HIV-1-infected patients are coinfected with HCV, suggesting that there are greater than 10 million coinfected individuals globally. Studies have demonstrated that the normal pathogenesis of HCV infection is significantly impacted by infection with HIV-1, with coinfected individuals possessing higher HCV viral loads, and more rapid progression to serious liver disease, including cirrhosis and hepatocellular carcinoma. Additionally, it has also been demonstrated that the efficacy of HCV therapy is decreased in HIV/HCV coinfected individuals. In a similar manner to HIV monoinfected patients, HIV/HCV coinfected patients have been shown to be increasing in age as therapies are getting more successful at extending the lifespan of infected individuals. However, mortality associated with liver disease still remains high in HIV-infected patients. In addition to direct liver effects caused by both HIV and HCV, coinfected patients are also at increased risk of cardiovascular disease, stroke, diabetes mellitus, and other comorbidities typically associated with aging.

Given these observations, the overall hypothesis of the proposed studies is that our laboratory is interested in determining whether HIV/HCV coinfection synergistically enhances the effects of age by accelerating immune system activation. These studies utilize molecular and cellular biology approaches to generate an overall picture of important pathways in HIV/HCV pathogenesis and to determine how age affects these pathways, and the potential relevance of coinfection to aging. Currently, we are quantifying and comparing immune activation profiles with gene expression profiles of adult and aged patients with respect to HIV/HCV coinfection to ascertain the effects that coinfection has with regard to chronic immune activation within aged patients. These studies are developing and utilizing unique HIV/HCV coinfected patient cohorts to determine the impact of age on human gene expression, immune activation, and development of neurocognitive impairment. These studies will impact research on HIV/HCV/Age by identifying new targets and strategies for anti-HIV-1 therapeutics and by minimizing the impact of both age and HCV on HIV-1 disease.

HIV-infection initiates a premature aging response

Figure 1. HIV-1 infection initiates a premature aging response. Normal aging-related disease states that are observed in the elderly occur at much younger ages in HIV-1-infected patients. These disease states include enhanced neurologic decline, metabolic/cardiovascular diseases including dyslipidemia, lipodystrophy, and diabetes, immune system dysfunction, and bone disease. Highly active antiretroviral therapy (HAART) also seems to play a role in premature aging.


Selected Publications

"Impact of age on markers of HIV-1 disease"
Pirrone V, Libon DJ, Sell C, Lerner CA, Nonnemacher MR, and B Wigdahl
Future Virology, 9(1):81-101, 2013.

"Substance abuse, HIV-1 and Hepatitis"
Parikh N, Nonnemacher MR, Pirrone V, Block T, Mehta A, and B Wigdahl
Current HIV Research, 10(7): 557-571, 2012.

"Impact of Tat genetic variation on HIV-1 disease"
Li L, Dahiya S, Kortagere S, Cunningham D, Pirrone V, Nonnemacher MR, and B Wigdahl
Advances in Virology: 123605, 2012.

"Antiviral Breadth and Combination Potential of Peptide Triazole HIV-1 Entry Inhibitors"
McFadden K, Fletcher P, Rossi F, Kantharaju F, Umashankara M, Pirrone V, Rajagopal S, Gopi H, Krebs FC, Martin-Garcia J, Shattock R, and I Chaiken
Antimicrobial Agents and Chemotherapy, 56(2): 1073-1080, 2012.

"Application and Removal of Polyanionic Microbicide Compounds Enhances Subsequent Infection by HIV-1"
Pirrone V, Passic SR, Wigdahl B, and FC Krebs
Virology Journal, 9: 33, 2012.

"Role of mu-opioids as cofactors in human immunodeficiency virus type 1 disease progression and neuropathogenesis"
Banerjee A, Strazza M, Wigdahl B, Pirrone V, Meucci O, and MR Nonnemacher
J. Neurovirol., 17(4): 291-302, 2011.

"Breaking the barrier: the effects of HIV-1 on the blood brain barrier"
Strazza M, Pirrone V, Wigdahl B, and MR Nonnemacher
Brain Research, 1399: 96-115, 2011.

"The rise and fall of polyanionic inhibitors of the human immunodeficiency virus type 1"
Pirrone V, Wigdahl B, and FC Krebs
Antiviral Research, 90(3): 168-182, 2011.

"Combinatorial approaches to the prevention and treatment of HIV-1 infection"
Pirrone V, Thakkar N, Jacobson JM, Wigdahl B, and FC Krebs
Antimicrobial Agents and Chemotherapy, 55(5): 1831-1842, 2011.

"Development of co-selected single nucleotide polymorphisms in the viral promoter precedes the onset of human immunodeficiency virus type 1-associated neurocognitive impairment"
Li L, Aiamkitsumrit B, Pirrone V, Nonnemacher MR, Wojno A, Passic S, Flaig K, Kilareski E, Blakey B, Ku J, Parikh N, Shah R, Martin-Garcia J, Moldover B, Servance L, Downie D, Lewis S, Jacobson JM, Kolson D, and B Wigdahl
J. Neurovirol., 17(1): 92-109, 2011.

"A styrene-alt-maleic acid copolymer is an effective inhibitor of R5 and X4 human immunodeficiency virus type 1 infection"
Pirrone V, Miller SR, Schlipf L, Ferguson ML, Kish-Catalone TM, Wigdahl B, Rando R, Labib ML, and FC Krebs
J. Biomed. Biotechnol., 2010: 548749, 2010.

"Innate and Adaptive Factors Regulating Human Immunodeficiency Virus Type 1 Genomic Activation"
Shah S, Nonnemacher MR, Pirrone V, and B Wigdahl
J Neuroimmune Pharmacol., 5(3): 278-293, 2010.

"Persistent interactions between biguanide-based compound NB325 and CXCR4 result in prolonged inhibition of human immunodeficiency virus type 1 infection"
Thakkar N, Pirrone V, Schlipf L, Ferguson ML, Miller SR, Wigdahl B, Labib ML, Rando R, and FC Krebs
Antimicrobial Agents and Chemotherapy, 54(5): 1965-1972, 2010.

"Specific interactions between the viral coreceptor CXCR4 and the biguanide-based compound NB325 mediate inhibition of human immunodeficiency virus type 1 infection"
Thakkar N, Pirrone V, Schlipf L, Ferguson ML, Miller SR, Wigdahl B, Labib ML, Rando, R, and FC Krebs
Antimicrobial Agents and Chemotherapy, 53(2): 631-638, 2009.

"Introducing metallocene into a triazole peptide conjugate reduces its off-rate and enhances its affinity and antiviral potency for HIV-1 gp120"
Gopi HN, Cocklin S, Pirrone V, McFadden K, Baxter S, Tuzer F, Zentner I, Krebs FC, and I Chaiken
Journal of Molecular Recognition, Special Issue, March 2008.

Contact Information

Research Office

Department of Microbiology & Immunology
245 N. 15th Street
Room 18105, MS 1013A
Philadelphia, PA 19102
Phone: 215.762.1289
Fax: 215.762.1955