Living or nonliving? Biological? Viruses Living or nonliving? Biological?

Virus Discovery Agents not seen with light microscope Pass through filters that trap bacteria (<0.2µm) Are these toxins or poisons? ”Virus” - Latin for “poison”

What is a Virus? Different from “living” MOs & cells Submicroscopic 18-350 nm Seen with electron microscope Obligate intracellular parasites No genes for metabolic machinery and energy ±Genes for nucleic acid synthesis Biochemically RNA or DNA, not both No small ions, polysaccharides (sugars) ±Virus modifided lipid membranes from host cell (enveloped viruses or naked viruses)

Animal Viruses

Virus Replication Kinetics Growth curve of bacteria and virus very different Virus - from assembly of pre-formed components MOs - from increase in sum of components, reproduce by cell division Viruses don’t “grow” or undergo division Bacterial growth curve Viral growth curve

Virus Nucleic Acid Single (ss) or double stranded (ds) RNA or DNA – genetic information Single (ss) or double stranded (ds) Linear, circular, or nicked Unsegmented (single molecule) or segmented (two or more moleclues) ssRNA may be plus (+) or minus (-) sense (+)RNA genome can serve as mRNA and directly translated into protein (-)RNA genome cannot serve as mRNA and cannot be translated directly into protein

Virus Genome

Virus Protein Capsomer - individual protein subunits of capsid Capsid – “coat”, outer structure made up of protein Capsomer - individual protein subunits of capsid Function of capsid: Protect nucleic acid from harsh environment Involved in attachment to host cell

Virus Capsid Two basic capsid structures: Icosahedral (spherical polygon) Helical (elongated rod)

Virus Envelope Naked virus - only nucleic acid and capsid Enveloped virus - outer lipid membrane layer Envelope from host cell membrane plus virus glycoprotein Enveloped human immunodeficiency virus (HIV)

Virus Exits Cell By Budding Enveloped virus acquire cell plasma membrane as exits host cell via budding Virus glycoprotein (ligand) in envelope play role in attachment to host cell (receptor) Mediate fusion of virus envelope with cell membrane during virus entry into host cell

Virus Infection and Attachment Host must contain cell receptor that virus binds to in initiating infection Virus ligand binds to cell receptor Ligand on capsid of naked virus and on outside of envelope virus gp 120 (the ligand) on HIV binds to CD4 (receptor) on T lymphocyte or CCR5 on macrophage

Virus Replication In A Host Cell Host cell must also have cellular metabolic machinery that virus needs for replication Host range of virus is spectrum of host cells that virus can infect and replicate in If virus successfully replicates in host cell, infection productive and host cell is permissive for virus If cell lacks something required for viral replication, infection abortive or non-productive and host cell is non-permissive for virus

Virus Replication Cycle Attachment - ligand on virus binds to receptor on host cell Penetration - virus gets inside host cell Naked virus: either receptor mediated endocytosis or formation of pore Enveloped virus: through fusion event Uncoating - separation of capsid and release of nucleic acid into cell cytoplasm or nucleus; preparation of viral transcription and nucleic acid replication Biosynthesis - viral proteins and viral nucleic acid replicated

Virus Biosynthesis RNA viruses - bring in own enzymes for transcribing mRNA and replicating their genome Cells do not contain enzymes for RNA as a template Most RNA viruses replicate in cytoplasm DNA viruses - either use host enzymes or bring in own enzymes to transcribe mRNA and replicate genome Retroviruses - unique RNA virus bring in enzyme called reverse transcriptase (RT) RT makes a dsDNA copy of viral ssRNA genome DNA then moves to nucleus where incorporated into cell DNA, then viral genes transcribe mRNA and translated

Virus Replication Cycle Assembly - viral components self-assemble into new viruses, occurs when sufficient number of viral proteins and viral genomes made Release - newly made virus exit host cell by lysis or budding

Classification of Virus One most commonly used virus classification is Baltimore scheme Based on relationship between viral genome and its mRNA needed for translation

Virus Infection and Pathology of Host Cell Even though can’t see virus, can see effects that virus has on host cell Death of cell – often occurs on release of virus Cytopathic effects – visible effects on cell caused by viral replication (plaques, rounded, syncytia) Cancer (cell transformation) – loss of cell growth control; require virus integrates all or part of genome into cell DNA

Overview of Virus Infectious Diseases By Organ Systems Skin and Soft Tissue Infections Ocular Infections Upper and Lower Respiratory Tract Infections (URTI, LRTI) Viremia and Sepsis Infections of Central Nervous System (CNS) Gastrointestinal Infections (GI) Sexually Transmitted Diseases (STD)

Skin and Soft Tissue Infections Warts (Papilloma virus) Smallpox (Variola virus) Chickenpox/Shingles (Varicella/Zoster virus) Measles (Rubeola virus) German measles (Rubella virus) Cold sores (Herpes Simplex virus)

Warts Human papilloma virus (dsDNA) Spread by direct contact Benign tumors with abnormal uncontrolled growth but stops after period of time Some infections result in cell transformation and malignant tumors Treated with acids or cryotherapy

Smallpox Variola virus (dsDNA) Transmitted by respiratory route Variola major (mortality >20%) Variola minor (mortality < 1%) Transmitted by respiratory route Virus moves from respiratory tract, bloodstream, skin to cause pustular rash that leaves scars Symptoms include fever, malaise, severe backache and abdominal pain WHO vaccination program successfully eradicated disease Use in bioterrorism?

Chickenpox and Shingles Varicella-zoster virus (herpesvirus, dsDNA) Infection via respiratory route Incubation ~ 2 weeks, but infected individual contagious at this stage Virus localizes in skin to cause vesicular rash with vesicles that fill with pus, rupture, and form scabs After chickenpox, virus remains latent in nerve cells and can be reactivated later in life to cause shingles (zoster)

Chickenpox and Shingles Shingles characterized by severe pain due to inflammation of sensory nerves around one side of nerve trunk Vaccine to prevent chickenpox now available

Measles Rubeola virus (paramyxovirus, ssRNA) Highly contagious Spread by respiratory route Incubation 10-12 days Symptoms similar to common cold plus papular rash (small, raised spots) Koplik spots (red patches with central white specks) in the oral cavity are diagnostic

Measles Severe complications include encephalitis, pneumonia, ear infections, and even death May later cause subacute sclerosing panencephalitis with progressive nerve destruction and death Vaccine available (part of MMR – Measles, Mumps, and Rubella) Often fatal infection of infants in developing countries due to underlying malnutrition with >1 million deaths/year

German Measles Rubella virus (Togavirus, ssRNA) Three day measles Transmitted via respiratory route Symptoms include slight fever and rash of small red spots Infection during first trimester of pregnancy can lead to birth defects (deafness, eye cataracts, heart defects, mental retardation) or death of the fetus Vaccination via MMR

Cold Sores Herpes Simplex virus (HSV), type I (dsDNA) Characterized by lesions of oral mucous membranes Following initial infection, virus remains latent in nerves Physical or emotional stress may cause reactivation of latent infection

Ocular Infections HSV, type I Corneal lesions Can lead to blindness or CNS invasion

Upper & Lower Respiratory Tract Infections Common cold Influenza

Common Cold Rhinoviruses (ssRNA) and Coronaviruses (ssRNA) >200 different types of rhinoviruses can cause common cold! Spread by respiratory secretions on hands and inhalation Symptoms include sneezing, nasal discharge, and congestion Emerging pathogen is SARS-CoV (Severe acute respiratory syndrome-Coronavirus)

Influenza Influenza virus (Orthomyxovirus, segmented, ssRNA) Transmitted via respiratory secretion Symptoms include fever, chills, headache, and general muscle aches Viruses are continually changing antigenic structure by “drift” and “shift” making it difficult to develop host immunity and effective vaccine Drift occurs by RNA mutation Shift occurs by genetic recombination or gene reassortment during dual infection of a host

Viremia & Sepsis Infectious mononucleosis - lymphocytes Blood and lymph systems Myocarditis – inflammation of heart muscle Infectious mononucleosis - lymphocytes Viral hemorrhagic fever – rash, fever

Myocarditis Commonly caused by Coxsackievirus (ss RNA) Caused by many different MOs Commonly caused by Coxsackievirus (ss RNA) Via respiratory route or GI tract Gains access to heart via bloodstream or lymphatics

Infectious Mononucleosis Epstein-Barr virus (Herpesvirus, dsDNA) Transmission via saliva, “kissing disease” Symptoms include fever, sore throat, swollen lymph nodes, general weakness Like all herpesvirus, after primary infection it remains latent, in B lymphocytes Linked to three cancers Hodgkins disease Burkitt’s lymphoma Nasopharyngeal carcinoma

Infections of CNS Meningitis and encephalitis Infection of membrane that cover brain and spinal cord and infection of brain By many different viruses Virus may enter through blood, and need to cross “blood-brain barrier” Other virus move along peripheral nerve into CNS Viral meningitis often called “aseptic meningitis” because no bacteria or fungi found in CSF Poliomyelitis Rabies

Poliomyelitis Poliovirus (Picornavirus, ssRNA) Three poliovirus serotypes Transmission occurs via GI tract after ingestion of fecal contaminated water Symptoms include fever, sore throat, and headache In 1-2% of cases virus penetrates capillary walls and enters CNS where it multiplies in motor nerve cells eventually killing them and causing paralysis Two vaccines used: Salk – wild type virus inactivated by formalin Sabin – oral, live, attenuated virus ( recent reactivation to virulence resulted in use of inactivated vaccine for first dose followed by two oral doses for infant vaccination)

Rabies Rabies virus (bullet-shaped Rhabdovirus, ssRNA) Transmission via saliva of rabid animal Virus travels along peripheral nerve to CNS where it causes encephalitis Symptoms include painful spasms of muscles of mouth and pharynx when swallowing liquids (hydrophobia) Treatment is with rabies immune globulin followed by active immunization

Viral Hemorrhagic Fever Caused by several different viruses Ebola virus causes this type of disease Transmitted from animal to human, then human to human Infects and destroys blood vessels High mortality rate from hemorrhaging and shock Natural animal host is unknown

GI Infections Mumps (parotitis) – salivary gland Hepatitis - inflammation of the liver Viral gastroenteritis – intestine

Mumps Mumps virus (Paramyxovirus, ssRNA) Transmission via salivary secretions and portal of entry is respiratory tract Incubation 16-18 days – during this time virus moves from respiratory tract, bloodstream, to parotid (salivary) gland and teste in males Symptoms include swelling, fever, painful swallowing, occasionally sterility Vaccination is via MMR

“Infectious” Hepatitis Hepatitis A virus (ssRNA) Transmitted via fecal-oral route Symptoms include anorexia, malaise, nausea, diarrhea, abdominal discomfort, fever and chills for 2-21 days Two-thirds of infected individuals have jaundice indicative of liver damage Recovery complete with no chronic disease

“Serum” Hepatitis Hepatitis B virus (dsDNA) Hepatitis C virus (ssRNA) Transmitted via body secretions (blood, saliva, STD) and needle sharing among drug abusers Incubation 4-26 weeks Symptoms range from subclinical to severe fever and headache with jaundice Most recover completely, but 10% chronic carriers with high incidence of liver disease and cancer Recombinant vaccine is available Hepatitis C virus (ssRNA) Disease and transmission similar to HBV No vaccine available

Viral Gastroenteritis In children, most commonly caused by rotavirus (dsRNA) or adenovirus (ds DNA) Symptoms include fever, diarrhea, vomiting In developing countries, high mortality among infants resulting in >1 million deaths/year due to underlying malnutrition and fluid loss

STD Genital herpes Genital warts

Genital Herpes Herpes simplex virus (HSV) type II (dsDNA) Incubation ~ 1 week Asymptomatic or symptoms of painful vesicular lesions containing infectious fluid Becomes latent in nerve cells and may be reactivated to cause same lesions in primary infection Can cross the placenta to infect fetus leading to mental retardation, defective sight and hearing Fetus can also be infected during delivery, therefore all women positive for this virus routinely deliver by C-section

Genital Warts Human papilloma viruses (dsDNA) Benign warts and tumors Some strains cause malignant tumors, cervical cancer Vaccine (Gardasil) for these virus strains to prevent cervical cancer

Subviral Particles: Prions Proteinaceous infectious particle No nucleic acid Self-replicating by misfolding of normal cellular protein Formerly called “slow viral infections” Neurological disease in mammals, transmissible spongiform encephalopathy (TSE), eventual death Kuru and Creutzfeldt-Jakob disease Scapie in sheep Bovine spongiform encephalopathy (Mad cow disease) Chronic wasting disease in deer and elk