Micro 615 Principals of Virology: Virus Structure, Classification, Detection & Persistence Alice Telesnitsky

I. What is a virus? A. A virus is a set of genes, either DNA or RNA, packaged in a protein-containing coat B. Viruses are obligate intracellular parasites capable of directing their own replication viruses are small

II. Examples of how viral infections are important in many A. Viruses cause diseases

HIV infection may become a common chronic condition

Polio Inapparent infection in 90-95% Abortive infection in 4-8% Major CNS involvement in 1-2% B. Can replicate in some humans without causing disease 1. Asymptomatic carriers with inapparent (subclinical) infection can transmit viral disease

B. Can replicate in some humans without causing disease, cont. 2. Viruses serve as co-factors for some diseases C. Significant in initiating disease in aging, immune-deficient (eg: transplant recipients) and other at-risk populations D. Virus-related entities such as endogenous retroelements 1. A significant portion of the human genome 2. Endogenous viruses can be mutagens and are a potential problem in xenografts E. Emerging viruses

III. Structural features of human viruses: from the inside out A. Genomes B. Capsids C. With or without envelop A virus is a set of genes, either DNA or RNA, packaged in a protein-containing coat

A. Genomes 1. RNA or DNA; single- or double-stranded; one or several segments 2. Small genomes--limited coding capacity B. Capsid morphologies 1. Helical Helical rods of a plant virus

Rabies: an enveloped helical virus Cartoon of rabies Rabies virus

2. Cubic---Icosahedral 20 triangular faces, 12 vertices adenovirus 3. Other example: “bullet-shaped” capsid of HIV

C. Exterior surface 1. Naked or enveloped 2. Physical properties affect transmission

IV. Virus classification small influenza HIV polio

DNA viruses small large

V. Assay and detection of viruses and their replication “viruses are obligate intracellular pathogens” A. Virus culture 1. Animals (or plants, bacteria, etc) 2. Tissue culture

B. Assays and detection 1. Plaque assay a. End point dilution b. Plaque forming units (PFU) 2. Agglutination 3. Infectivity eg: LD Cytopathic effect (CPE) syncytia

4. Other ways of measuring virus a. Count particles by electron microscope Viruses differ in infectious units per biochemical unit

VI. General types of viral infections A. Acute clinical disease 1. Localized virus replication at site of infection 2. Disseminated spread to and replication in secondary sites B. Persistent infections on organism level 1. Chronic infections eg: acute phase disease followed by “smoldering infection” sometimes seen for adenovirus 2. Latent infections eg: herpes 3. Others

C. Viral persistence on cellular level

VII. Biology of herpes viruses A. Biology 1. Large enveloped DNA viruses 2. Possess many genes 3. Replication involves acute and latent phases B. Human infection by Herpes simplex virus I 1. Acute phase disease 2. Latency a. Physiology of virus and of cell during latency b. Immune response avoidance 3. Reactivation

C. Other human Herpes viruses 1. HSV-II 2. Varicella-Zoster (VSV) Chicken pox and shingles 3. Cytomegalovirus (CMV) a. Epidemiology b. Prenatal infection c. Transplant mortality

4. Epstein Barr virus a. Discovery and association with Burkitt's lymphoma Environmental cofactors? b. Primary infection (mononucleosis) c. Association with other malignancies 5. HHV-6 (roseola); HHV-7 6. Kaposi's Sarcoma Herpes Virus (KSHV)/HHV-8 a. Epidemiology and prevalence HIV an environmental co-factor b. Primary disease unknown