Natalia Smirnova, PhD
Office: W117 ARBL Building, Foothills Campus
My research interests include studying the intricate mechanisms of the immune response to the pathological state of the organism, such as infectious diseases, autoimmune disorders, and cancer. The most recent focus of my research is Bovine Viral Diarrhea Virus (BVDV) from family Flaviviridae: affecting cattle herds, it causes significant economic impact on the agriculture world-wide.
Many important questions related to the mechanisms of fetal persistent infections and their consequences for the health of the mother and fetus in both animal and human diseases remain unanswered. BVDV belongs to the group of viruses, able to cause intrauterine persistent infection in developing fetuses. Transplacental infection with non-cytopathic Bovine Viral Diarrhea Virus (ncpBVDV) during the first 150 days of bovine pregnancy leads to fetal persistent infection with chronic life-long viremia and growth retardation. Infection with BVDV in late gestation is transient and cleared by both maternal and fetal immune systems. Development of persistent infection is one of the strategies utilized by viruses to evade the immune response of the host and to establish a reservoir of infection in a population. Animals persistently infected with BVDV serve as a continuous source of the virus due to life-long shedding. Search for biomarkers distinguishing cows with persistently infected with BVDV fetuses represents one of the practical directions of the ongoing study.
The other direction is studying aspects of the maternal and fetal response to BVDV infection. We have shown that: (i) infection with ncpBVDV induces a vigorous type I IFN response in transiently infected animals and late-gestation fetuses, (ii) BVDV infection causes low-grade chronic type I IFN response in persistently infected fetuses and born calves, and (iii) presence of a persistently infected fetus causes down-regulation of proinflammatory signaling pathways in the blood of the dam (e.g. CXCR4 and T-cell receptor pathways), which could have deleterious consequences on fetal development and immune responses. We also have found indications that thyroid system of the dam can be compromised by presence of the persistently infected fetus, which could affect maternal and fetal metabolism, compromising fetal development and health of the dam.
Hansen TR*, Smirnova NP*, Van Campen H, Shoemaker ML, Ptitsyn AA, Bielefeldt-Ohmann H. 2010. Maternal and fetal response to fetal persistent infection with Bovine Viral Diarrhea Virus. Am J Reprod Immun 64:295-306.
*Hansen and Smirnova are co-first authors.
Smirnova NP, Ptitsyn AA, Austin KJ, Bielefeldt-Ohmann H, Van Campen H, Han H, van Olphen AL, Hansen TR. 2009. Persistent fetal infection with bovine viral diarrhea virus differentially affects maternal blood cell signal transduction pathways. Physiol Genom 36(3):129-139.
Shoemaker ML, Smirnova NP, Bielefeldt-Ohmann H, Austin KJ, van Olphen A, Clapper JA, Hansen TR. 2009. Differential expression of the type I Interferon pathway during persistent and transient bovine viral diarrhea virus infection. J Interferon Cytokine Res 29:23-36.
Oliveira JF, Henkes LE, Ashley RL, Purcell SH, Smirnova NP, Veeramachaneni DN, Anthony RV, Hansen TR. 2008. Expression of interferon (IFN)-stimulated genes in extrauterine tissues during early pregnancy in sheep is the consequence of endocrine IFN-(tau) release from the uterine vein. Endocrinology 149:1252-1259.
Bielefeldt-Ohmann H, Tolnay A-E, Reisenhauer CE, Hansen TR, Smirnova N, Van Campen H. 2008. Transplacental infection with non-cytopathic bovine viral diarrhea virus type I and II: viral spread and molecular neuropathology. J Comp Pathol 138(2-3):72-85.
Smirnova NP, Bielefeldt-Ohmann H, Van Campen H, Austin KJ, Han H, Montgomery DL, Shoemaker ML, van Olphen AL, Hansen TR. 2008. Acute non-cytopathic bovine viral diarrhea virus infection induces pronounced interferon type I response in pregnant cows and fetuses. Virus Res 132:49-58.
Smirnova N, Troyer JL, Schissler J, Terwee J, Poss M, VandeWoude S. 2005. Feline lentiviruses demonstrate differences in receptor repertoire and envelope structure elements. Virology 342:60-76.
Yunker VM, Smirnova NP, Ustinov AS. 1995. The role of macrophage suppressor activity in metastatic spreading following tumor resection. Voprosy Onkologii 41(1):64-69 (in Russian).
Yunker VM, Taraskina NP, Ustinov AS. Participation of macrophages in the mechanism mediating the enhancement of metastasis formation after tumour resection. Biomed Sci 2:569-575.