Virology

Dr. Peter C. Angeletti

SCHOOL OF BIOLOGICAL SCIENCES

HPV replication, encapsidation, and pathogeneses

Research Interests:  Dr. Angeletti’s research is focused on topics relating to sexually transmitted Human papillomaviruses (HPVs). The first topic involves the analysis of cis and trans-acting signals required for stable replication of HPVs.  A second topic of interest is the analysis of the packaging requirements for HPVs.  More recently, Dr. Angeletti has begun cervical cancer screening studies in Tanzania, which is funded by the National Cancer Institute (NCI).  Another area of study is the role of HPV in ocular surface squamous neoplasm (OSSN) in the sub-Saharan African country of Zambia.  In these studies, Angeletti looks at the affect of HIV upon formation of HPV-related neoplasms.

Dr. Lindsey Crawford

DEPARTMENT OF BIOCHEMISTRY

Cytomegalovirus Infection and influence on Hematopoietic Stem Cell Fate

Dr. Crawford's laboratory studies how viruses manipulate the human immune system. We address questions looking at how chronic viruses infect and control hematopoietic stem cells (the fundamental “parent” cell for all immune cells). Ongoing projects use biochemistry, virology, immunology, and stem cell biology approaches to address questions in viral pathogenesis, herpesvirus latency and reactivation, hematopoietic stem cell fate, and immune system differentiation.

A main focus of the lab is in determining how HCMV (human cytomegalovirus, a common human herpesvirus) exploits cellular traits to establish latency, maintain a viral reservoir, control reactivation, and manipulate hematopoiesis which will help develop novel targeted treatments, a more detailed understanding of hematopoietic mechanisms, and an improved understanding of immune cell fate during viral infection.

Dr. Hernan Garcia-Ruiz

PLANT PATHOLOGY

Plant-virus interactions, anti-viral RNA silencing, RNA virus replication and their interconnections

Hernan is a virologist interested in the molecular mechanisms of viral RNA replication and in antiviral RNA silencing. Hernan comes to UNL from the Donald Danforth Plant Science Center, where he was a research scientist. Hernan completed his postdoctoral work at the Oregon State University Center for Genomics and Biocomputing, with support from a Helen Hay Whitney fellowship. At UNL Hernan is the State Virologist and will teach a Molecular Virology class. Initial research will focus on the interconnection between RNA replication and RNA silencing mechanisms in viruses using yeast and plants as model systems in combination with genomic and bioinformatics approaches.

Dr. Qingsheng Li

SCHOOL OF BIOLOGICAL SCIENCES

Understanding of the interaction of HIV-1 with its host during mucosal transmission, and development of anti-viral topical microbicide and vaccine

Research Interests: Qingsheng’s research focuses on better understanding the interaction of human immunodeficiency virus type-1 (HIV-1) with its host in the earliest infection to elucidate key steps and critical events in the mucosal transmission of HIV-1, to identify correlates of protection, and ultimately to develop an effective anti-viral topical microbicide and vaccine.

Dr. Fernando Osorio

SCHOOL OF VETERINARY MEDICINE & BIOMEDICAL SCIENCES

Tropism, immunopathogenesis, and vaccinology of porcine reproductive and respiratory syndrome virus (PRRSV) a major pathogen of swine

My research centers on pathogenesis of and immune response to viral infections. Due to the significance of the subject for U.S. animal agriculture, we focus on a major viral agent that affects swine: Porcine Reproductive and Respiratory Syndrome Virus (PRRSV, an arterivirus, ssRNA+ genome).

Dr. Asit Pattnaik

SCHOOL OF VETERINARY MEDICINE & BIOMEDICAL SCIENCES

Replication and pathogenic mechanisms of RNA viruses

Studies in my laboratory focus on molecular biology and immunopathogenesis of two different viral pathogens, the vesicular stomatitis virus (VSV), a non-segmented negative-strand RNA virus in the family Rhabdoviridae and order Mononagavirales, and the porcine reproductive and respiratory syndrome virus (PRRSV), a positive-strand RNA virus in the family Arteriviridae and order Nidovirales. VSV has served as an excellent paradigm for many negative-strand RNA viruses (some of which are important human pathogens, such as respiratory syncytial, rabies, measles, and parainfluenza, hemorrhagic bunya and arenaviruses) to understand the basic mechanisms of the genetic expression of this group of viruses. PRRSV is an economically important pathogen, causing serious diseases in swine worldwide. Understanding the mechanism(s) of gene expression and its regulation as well as pathogenesis is essential for identifying virus-specific targets for therapeutic intervention in controlling infection by these viruses.

Dr. Thomas Petro

DEPARTMENT OF ORAL BIOLOGY, COLLEGE OF DENTISTRY

Role of IRF-3 in pathogenesis, as well as innate and adaptive immunity during Theiler’s Virus infection

All humans are infected with viruses throughout their lifetime. While most of these virus infections stimulate innate and adaptive immunity and are eliminated, it is estimated that each human is infected by 8-10 viruses that persistently stimulate the immune systems and are never eliminated. It is hypothesized that in some cases these persistent viral infections lead to diseases, such as Multiple Sclerosis (MS). As a model for persistent viral infections, his laboratory is focusing upon the innate immune response to the Theiler's Murine Encephalomyelitis Virus (TMEV). In some strains of mice, TMEV persistently infects macrophages of the immune system but is never eliminated within the lifetime of the individual mouse. Those mice strains end up with demyelination and symptoms like MS. In other strains of mice, TMEV is eliminated within a few weeks. However, the immune response to eliminate the virus is not without consequence and these mice end up with damage to the hippocampus region of the brain. We showed that failures within the innate immune system are causes of TMEV persistence but also protect the mice from immune mediated damage to host tissues.

The innate immune response to viral infection depends on Interferon Response Factor-3 (IRF-3), which plays a key role in induction of Type I interferons (IFN-alpha/beta), IL-6, and IL-12. We showed that IL-6 induces activation of STAT1 and ERK and thus is a key antiviral cytokine during this response to TMEV. We hypothesize that robust activation of IRF3 induces a high level of IL-6 expression that contributes to viral control but also causes damage to the hippocampus. We have shown that functional IRF3 is related to viral clearance but is also related to hippocampal damage. In addition to innate cytokine production, IRF-3 is also involved in the induction of apoptosis (programmed cell death) that is triggered in virus-infected cells. Apoptosis prevents viral persistence and infection into surrounding cells. We have also found that IRF-3 of mice that cannot eliminate TMEV differs from IRF-3 of mice that can control this virus, in that it cannot participate in virus induced apoptosis as well. Therefore our central hypothesis is that differences in host IRF-3 underlie persistent infections with certain viruses but also immune mediate damage during viral infections.

Dr. N R Jayagopala Reddy

SCHOOL OF VETERINARY MEDICINE & BIOMEDICAL SCIENCES

Cellular and molecular mechanisms of auto-immunity

Most healthy individuals have a propensity to develop autoimmune diseases, as evidenced by the presence of autoreactive T cells in their naïve periphery. T cells are educated in the thymus, where high-affinity T cell receptor (TCR)-bearing cells that interact with self-antigens are deleted by negative selection, while T cells with low-affinity TCR to self-antigens are selected positively and exported to the periphery. In spite of the presence of self-reactive T cells in the naïve peripheral repertoires, autoimmune responses do not ensue spontaneously. How this tolerance is maintained is a fundamental question. It has been suggested that the environmental antigens that bear similarities to self-antigens break self-tolerance by cross-reactivity. To this end, we focus our investigations on the identification of microbial products that can potentially induce autoimmunity in the heart and immunologically privileged sites such as the central nervous system and eyes through antigenic mimicry. Mechanistically, we are particularly interested in delineating the role of antigen-specific T cells in the autoimmune diseases of infectious origin.

Dr. Nicole Sexton

SCHOOL OF BIOLOGICAL SCIENCES

Evolution and Spread of Arboviruses

Arboviruses are prevalent and persistent human health threats across the globe. Additionally, many arboviruses including Zika, chikungunya, Dengue, Japanese encephalitis, and Rift Valley fever viruses have emerged in new host species or geographical locations demonstrating an ability to adapt to new environments and host. However, what allows for the efficient spread of arboviruses despite high mutation rates, and what prevents some insect specific viruses from becoming infectious in vertebrates is not understood. Dr. Sexton’s research investigates mechanisms of efficient spread by arboviruses and virus traits associated with host preferences.

Dr. James Van Etten

PLANT PATHOLOGY

Characterization of large dsDNA viruses that infect certain chlorella-like green algae

Research in the Van Etten laboratory focuses on the isolation and characterization of large icosahedral, dsDNA-containing, plaque-forming viruses that infect certain unicellular, eukaryotic chlorella-like green algae.  These viruses are ubiquitous in fresh water from all over the world. The chlorella viruses have genomes as large as 370 kb that contain as many as 400 protein encoding- and 16 tRNA encoding-genes.  Besides their large genomes, the chlorella viruses have other unexpected features: (i) They encode multiple DNA methyltransferases and DNA restriction endonucleases.  (ii) Unlike other glycoprotein-containing viruses, chlorella viruses encode most, if not all, of the components required to glycosylate their proteins.  (iii) Many chlorella virus-encoded proteins are either the smallest or among the smallest proteins of their class.  Consequently, these proteins serve as models for mechanistic and structural studies.  Infection by the chlorella viruses resembles bacterial infection by tailed bacteriophages in many respects.

Dr. Hiep Vu

DEPARTMENT OF ANIMAL SCIENCE

Immune response against porcine respiratory and reproductive syndrome virus (PRRSV), and development of vaccines

My laboratory studies two important viruses of swine: porcine reproductive and respiratory syndrome virus (PRRSV) and influenza A virus of swine (IAV-S). The research topics that are studied in my laboratory include: (i) Host immune responses to natural infection or vaccination, (ii) Molecular characteristics of the viruses currently circulating in the swine population, and (iii) Viral proteins and/or epitopes capable of eliciting protective immunity. Collectively, results obtained from these studies will be valuable for the optimal design safe and effective vaccines against divergent viral strains circulating in the field.

Dr. Eric Weaver

SCHOOL OF BIOLOGICAL SCIENCES

Adenovirus vector for vaccine against influenza and other viruses

My current research explores the use of bioinformatics, phylogenetics, immunology and molecular biology to study the basic mechanisms of host-pathogen interactions and to create improved vaccines against microbial diseases. My research program can be broken into two arms, vaccine antigen design and vaccine platform design. First, we are testing ancestral/centralized genes to determine if they are useful as universal vaccines  in vivo.  In addition we are exploring systems biology approaches to improve vaccine antigen design to improve the breadth and efficacy of the vaccine antigens. Second, vaccine platform design explores the use of alternative viral vectors as vaccines, as well as the development of safer more effective viral vaccine platforms.

Dr. Matthew Wiebe

SCHOOL OF VETERINARY MEDICINE & BIOMEDICAL SCIENCES

Understanding intracellular defenses against foreign DNA by using poxvirus-infected cell models

One of the most fundamental questions in the field of immunology is how our immune system identifies an invading pathogen as “foreign” rather than “self”.  When this decision is made correctly growth of the virus or bacteria can kept at a minimum.  However, failure to recognize an invader extends the amount of damage it may produce or, if self is incorrectly regarded as foreign, then autoimmune disease occurs.  While significant progress has been made toward identifying viral and bacterial components which are found to be “foreign” and activate the immune system, much remains to be learned.

Dr. Shi-hua Xiang

SCHOOL OF VETERINARY MEDICINE & BIOMEDICAL SCIENCES

HIV envelope glycoprotein structure, function, vaccine design, and utilizing commensal bacteria for anti-HIV infection

Human immunodeficiency virus type 1 (HIV-1) is the etiologic agent of AIDS (Acquired Immune Deficiency Syndrome).  About thirty years after identification of HIV as the causative agent of AIDS, the AIDS epidemic remains a global health issue.  Our research interests are focused on HIV/AIDS, with the ultimate goal of developing an effective vaccine or a long-term preventive strategy to counter this devastating pandemic.  In addition, we are also working on small ruminant lentviruses (SRLV) and try to find the genetic resistant-forms against SRLV infection.

The current major projects in our laboratory are described below.

I. Envelope Structure and Viral Entry

Human immunodeficiency virus type 1 (HIV-1) is the etiologic agent of AIDS (Acquired Immune Deficiency Syndrome).  About thirty years after the identification of HIV as the causative agent of AIDS, the AIDS epidemic remains a global health issue.  Our research interests are focused on HIV/AIDS, with the ultimate goal of developing an effective vaccine or a long-term preventive strategy to counter this devastating pandemic.  In addition, we are also working on small ruminant lentiviruses (SRLV) and try to find the genetic resistant-forms against SRLV infection.  The current major projects in our laboratory are described below.

II. Envelope Structure and Viral Entry

HIV-1 is an enveloped virus, requiring for cell entry a membrane fusion process mediated by the interactions of viral envelope glycoproteins (gp120 and gp41), a primary receptor CD4, and a chemokine coreceptor (CCR5 or CXCR4). Viral entry is a critical step for establishing infection, thus providing a powerful incentive to understand the intricate biochemical mechanisms of viral entry as a prerequisite for developing effective antiviral therapies. The interaction of HIV-1 gp120 and the CD4 receptor has been well characterized. However, the interactions between viral envelope glycoproteins and the HIV co-receptor (CCR5 or CXCR4) are poorly understood. For example, it is not clear how the HIV gp120 core and V3 loop contact the N-terminal and extracellular loops of CCR5 to facilitate the entry process, nor has the molecular structure of CCR5 been elucidated. We will investigate the interactions between gp120 and the coreceptor CCR5 or CXCR4, employing various molecular and cellular approaches to dissect these associations in more detail.

III. Envelope-Based AIDS Vaccine Development

The HIV-1 envelope has evolved such an immunosuppressive state that does not provoke adequate immunogenicity to trigger the production of neutralizing antibodies. Therefore, our research objective is to improve the immunogenicity of the HIV-1 envelope. The approach involves stabilizing a CD4-bound conformation of gp120, in which CD4 as well as the co-receptor (CCR5 or CXCR4) binding sites are exposed. These two sites are the most conserved regions in the HIV-1 Env. This gp120 antigenic conformation should induce a much stronger immune response, and consequently, elicit more potent neutralizing antibodies.

Another approach involves epitope-based antigen design. Epitope information gleaned from studies of known neutralizing antibodies such as VRC01, b12 or 2G12 should facilitate fragment structure-based design. We anticipate that a small epitope might elicit potent neutralizing antibodies against the virus.

Dr. Luwen Zhang

SCHOOL OF BIOLOGICAL SCIENCES

Herpesvirus-host interactions in innate immunity and cancer formation

Research Interests:  Dr. Luwen Zhang’s laboratory studies the transformation processes. Epstein-Barr virus is (EBV) a human herpesvirus of increasing medical importance. EBV infection has been associated with the development of several human cancers. In immunocompromised individuals, such as organ transplant recipients or AIDS patients, EBV almost certainly causes two fatal cancers: post-transplantation lymphoproliferative disorder (PTLD) and AIDS-associated central nerve system (CNS) lymphoma.  The Zhang lab tackles the problems related to how virus interacts with cell, and transforms normal cells into cancerous ones.  Also, potential treatment of human cancers is also on their agenda. Zhang lab has been testing a novel approach to specifically block the viral transformation events that lead to the development of human cancers.