Pathogenic RNA Viruses 25 Pathogenic RNA Viruses

RNA Viruses Only agents that store genetic information in RNA molecules RNA viruses are categorized by several factors Their genomic structure Presence of an envelope Size and shape of their capsid Four types of RNA viruses Positive single-stranded RNA (+ssRNA) Retroviruses (+ssRNA viruses that convert their genome to DNA) Negative single-stranded RNA (–ssRNA) Double-stranded RNA (dsRNA) Positive RNA can be used by a ribosome to translate protein Negative RNA transcribed as mRNA to be processed by a ribosome

Naked, Positive ssRNA Viruses Picornaviridae Smallest of the animal viruses Large family that contains many human pathogens Picornaviruses that cause human disease are in several genera Rhinovirus, Enterovirus, and Hepatovirus Caliciviridae, Astroviridae, and Hepeviridae Larger than picornaviruses Cause gastrointestinal disease

Figure 25.1 Rhinoviruses (stained orange), the most common cause of colds. 4

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Naked, Positive ssRNA Viruses Common Colds Caused by Rhinoviruses Epidemiology of Rhinovirus infections Rhinoviruses cause most cases of the cold Infections limited to the upper respiratory tract A single virus is often sufficient to cause a cold Virus transmitted by aerosols, fomites, or hand-to-hand contact Most commonly transmitted by direct person-to-person contact People acquire some immunity against serotypes that have infected them The number of infections tends to decrease with age

Naked, Positive ssRNA Viruses Diseases of the Enteroviruses Transmitted via the fecal-oral route Infect the pharynx and intestine Spread via the blood, infecting various cells in the body Enteroviruses kill their host cells Three main enteroviruses Polioviruses, coxsackieviruses, and echoviruses

Naked, Positive ssRNA Viruses Diseases of the Enteroviruses Poliomyelitis Postpolio syndrome Crippling deterioration in the function of polio-affected muscles Near elimination of polio due to development of two vaccines Inactivated polio vaccine (IPV) Developed by Jonas Salk Oral polio vaccine (OPV) Developed by Albert Sabin

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Naked, Positive ssRNA Viruses Diseases of the Enteroviruses Other diseases of enteroviruses Coxsackieviruses and echoviruses also cause human disease Infection occurs via the fecal-oral route Most infections are subclinical or produce mild symptoms

Naked, Positive ssRNA Viruses Diseases of the Enteroviruses Other diseases of enteroviruses Coxsackie A viruses Produce self-limiting lesions and fever Herpangina Hand-foot-and-mouth disease Acute hemorrhagic conjunctivitis Cause some colds

Naked, Positive ssRNA Viruses Diseases of the Enteroviruses Other diseases of enteroviruses Coxsackie B viruses Associated with myocarditis and pericardial infections Also causes painful disease called pleurodynia Can cross the placenta and cause disseminated disease Both coxsackie A and B viruses can cause meningitis Echoviruses Acquired intestinally Can cause meningitis and colds

Figure 25.5 Lesions characteristic of hand-foot-and-mouth disease. 13

Naked, Positive ssRNA Viruses Diseases of the Enteroviruses Epidemiology of Enterovirus infections Worldwide distribution Often occur in areas with inadequate sewage treatment Infection occurs through fecal-oral route Ingestion of contaminated food or water Contact with infected hands or fomites Most enteroviruses pose greatest risk to fetuses and newborns

Naked, Positive ssRNA Viruses Hepatitis A Hepatitis A virus is the causative agent Survives on various surfaces and is resistant to common household disinfectants Transmitted through the fecal-oral route Signs and symptoms are due to the patient's immune response Include fever, fatigue, nausea, anorexia, and jaundice Infection does not cause chronic liver disease Complete recovery occurs most of the time Vaccine is available for children and adults

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Naked, Positive ssRNA Viruses Acute Gastroenteritis Caliciviruses and astroviruses can cause acute gastroenteritis Can cause outbreaks in day care centers, schools, and hospitals Caliciviruses cause diarrhea, nausea, and vomiting Noroviruses cause most cases of viral gastroenteritis Astroviruses cause diarrhea but no vomiting No specific treatment except replacement of fluid and electrolytes Prevention involves adequate sewage and water treatment, frequent handwashing, and disinfection of contaminated surfaces

Naked, Positive ssRNA Viruses Hepatitis E Also known as enteric hepatitis Caused by hepatitis E virus Formerly classified as a calicivirus Fatal in 20% of pregnant women The disease is self-limiting Prevent by interrupting the fecal-oral route of transmission

Enveloped, Positive ssRNA Viruses Togaviridae and Flaviviridae Enveloped, icosahedral +ssRNA viruses Arboviruses Transmitted by arthropods Coronaviridae Enveloped, helical +ssRNA viruses

Enveloped, Positive ssRNA Viruses Diseases of +RNA Arboviruses Zoonoses Animal diseases that spread to humans Mosquitoes and ticks transmit arboviruses among animal hosts Arthropod vectors remain infected Are a continual source of new infections Humans are dead-end hosts for these viruses Most infections result in mild, flulike symptoms Arboviruses can occasionally result in second-stage infections Encephalitis, dengue fever, and yellow fever

Enveloped, Positive ssRNA Viruses Diseases of +RNA Arboviruses Encephalitis Different togaviruses cause encephalitis in horses and humans Eastern equine encephalitis (EEE) Western equine encephalitis (WEE) Venezuelan equine encephalitis (VEE) Normal host is either a bird or a rodent EEE causes most severe disease in humans West Nile virus Flavivirus introduced to the U.S. in 1999 Asymptomatic in most cases Severe cases may cause encephalitis

Figure 25.9 Hosts and transmission of viruses of equine encephalitis and West Nile encephalitis. 22

Enveloped, Positive ssRNA Viruses Diseases of +RNA Arboviruses Dengue fever Flavivirus transmitted by Aedes mosquitoes Endemic in Asia, South America, and Mexico Disease occurs in two phases Initially causes fever, weakness, edema, and severe pain Second phase causes bright rash and return of the fever Dengue hemorrhagic fever can occur following reinfection Causes internal bleeding, shock, and possibly death No treatment is available

Enveloped, Positive ssRNA Viruses Diseases of +RNA Arboviruses Yellow fever Disease involving degeneration of the liver, kidneys, and heart Caused by a flavivirus Mortality can approach 20% Eliminated in the U.S. through vaccination and mosquito control Still remains a significant cause of death worldwide

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Enveloped, Positive ssRNA Viruses Other Diseases of Enveloped +ssRNA Viruses Rubella Also called "German measles" Rubella virus is the causative agent One of the five childhood diseases that produces skin lesions Infection begins in respiratory system but spreads throughout the body Characterized by a rash of flat, pink to red spots Infections in children are usually not serious Adults can develop arthritis or encephalitis Infection of pregnant women can cause congenital defects Vaccination effective at reducing the incidence of rubella

Enveloped, Positive ssRNA Viruses Other Diseases of Enveloped +ssRNA Viruses Hepatitis C Caused by hepatitis C virus (HCV) Accounts for about 20% of hepatitis cases in the United States Spread through needles, organ transplants, and sexual activity Chronic infection with few if any symptoms Severe liver damage and liver failure can occur over time Alpha interferon, protease inhibitors, and ribavirin can reduce the number of hepatitis C viruses in some patients No vaccine is available

Enveloped, Positive ssRNA Viruses Other Diseases of Enveloped +ssRNA Viruses Diseases of coronaviruses Named for the corona-like halo formed by their envelopes Transmitted via large droplets from the upper respiratory tract Second most common cause of colds Severe acute respiratory syndrome Emerging disease caused by previously unknown coronavirus Causes high fever, headache, and respiratory distress No treatment or vaccine is available Quarantine of infected individuals and use of face masks helps prevent SARS

Enveloped, Positive ssRNA Viruses with Reverse Transcriptase Retroviruses Studied more than any other group of viruses Have polyhedral capsids with spiked envelopes Genomes contain two identical molecules of positive ssRNA Retroviruses don't conform to the "central dogma" Retroviruses transcribe dsDNA from ssRNA using reverse transcriptase Two types of retroviruses Viruses that are primarily oncogenic Viruses that are primarily immunosuppressive

Enveloped, Positive ssRNA Viruses with Reverse Transcriptase Oncogenic Retroviruses (Deltaretrovirus) Human T-lymphotrophic virus 1 (HTLV-1) Identified in patient with adult acute T-cell lymphocytic leukemia Tax protein activates cell growth genes in helper T cells HTLV-2 causes a rare cancer called hairy-cell leukemia HTLV-5 has not been linked to cancer HTLV-1 and HTLV-2 are transmitted via sexual intercourse, blood transfusion, and contaminated needles No specific antiviral treatment Infections are chronic, and long-term prognosis of patients is poor Infections prevented with same behavior changes needed to prevent HIV

Enveloped, Positive ssRNA Viruses with Reverse Transcriptase Immunosuppressive Retroviruses (Lentivirus) and Acquired Immunodeficiency Syndrome Acquired immunodeficiency syndrome (AIDS) Not a disease but a syndrome Defined as certain opportunistic or rare infections along with infection by HIV or a severe decrease in the number of helper T cells and a positive test for HIV Several infections and diseases define AIDS Two major types of HIV HIV-1 is prevalent in the United States and Europe HIV-2 is prevalent in West Africa

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Enveloped, Positive ssRNA Viruses with Reverse Transcriptase Immunosuppressive Retroviruses (Lentivirus) and Acquired Immunodeficiency Syndrome Structure of HIV Several infections and diseases define AIDS Two antigenic glycoproteins found in the viral envelope gp120 Primary attachment molecule of HIV Exhibits antigenic variability during prolonged infection gp41 Promotes fusion of the viral envelope to target cell Viral characteristics impede immune clearance of HIV

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Enveloped, Positive ssRNA Viruses with Reverse Transcriptase Immunosuppressive Retroviruses (Lentivirus) and Acquired Immunodeficiency Syndrome Origin of HIV Likely arose from mutation of simian immunodeficiency virus (SIV) May have emerged in the human population around 1930 Whether the two HIV types are derived from the same or different SIV strains is unknown

Enveloped, Positive ssRNA Viruses with Reverse Transcriptase Immunosuppressive Retroviruses (Lentivirus) and Acquired Immunodeficiency Syndrome Details of synthesis and latency Reverse transcriptase transcribes dsDNA from ssRNA Antigenic variants of HIV result from errors introduced in the genome during transcription dsDNA provirus enters the nucleus Viral integrase inserts provirus into a human chromosome Integrated DNA passed to progeny cells during replication Provirus can remain dormant for years Macrophages and monocytes are major reservoirs of HIV

Enveloped, Positive ssRNA Viruses with Reverse Transcriptase Immunosuppressive Retroviruses (Lentivirus) and Acquired Immunodeficiency Syndrome Details of release, assembly, and maturation HIV exits cell at lipid rafts in the cytoplasmic membrane Lipid raft components become the viral envelope Capsomeres form immature capsid outside the cell Viral protease releases proteins that produce a mature virus Protease inhibitors used to treat HIV Pathogenesis of AIDS Only humans replicate HIV HIV destroys the immune system

Figure 25.22 Some diseases associated with AIDS. 38

Enveloped, Positive ssRNA Viruses with Reverse Transcriptase Immunosuppressive Retroviruses (Lentivirus) and Acquired Immunodeficiency Syndrome Epidemiology of AIDS AIDS first recognized in young male homosexuals in the U.S. AIDS is now found worldwide HIV found in blood, semen, saliva, vaginal secretions, and breast milk can cause infections Blood and semen more infective than other secretions Infected fluid must be injected or contact a tear or lesion in the skin or mucous membranes

Enveloped, Positive ssRNA Viruses with Reverse Transcriptase Immunosuppressive Retroviruses (Lentivirus) and Acquired Immunodeficiency Syndrome Epidemiology of AIDS Some behaviors increase the risk of HIV infection Anal intercourse Sexual promiscuity Intravenous drug use Intercourse with someone in these categories A few cases of casual HIV spread have been documented

Enveloped, Unsegmented Negative ssRNA Viruses Paramyxoviridae Multinucleate syncytia enable virus to evade the immune system Four genera infect humans Morbillivirus (measles virus) Respirovirus (parainfluenza viruses) Rubulavirus (mumps virus) Pneumovirus (respiratory syncytial virus) Rhabdoviridae Include a variety of plant and animal pathogens Rabies is the most significant pathogen Filoviridae Cause a number of emerging diseases

Enveloped, Unsegmented Negative ssRNA Viruses Measles One of five classical childhood diseases Also called rubeola One of the more contagious childhood infections Causes more serious disease than rubella

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Enveloped, Unsegmented Negative ssRNA Viruses Measles Epidemiology of measles infections Spread in the air via respiratory droplets Viral spread requires large, dense populations of people Viruses infect the respiratory tract, then spread through the body Koplik's spots appear on the mucous membrane of the mouth Lesions then appear on the head and spread over the body Rare complications of measles can result Pneumonia, encephalitis, and subacute sclerosing panencephalitis (SSPE) Vaccine has eliminated endemic measles in the United States

Enveloped, Unsegmented Negative ssRNA Viruses Measles Diagnosis, treatment, and prevention of measles Diagnosis Signs of measles, particularly Koplik's spots, are diagnostic Treatment No antiviral treatment is available Prevention Vaccine administered in infancy and again before grade school Measles still a frequent cause of death in other countries

Enveloped, Unsegmented Negative ssRNA Viruses Diseases of Parainfluenza Virus Four parainfluenza viruses (HPIV) cause respiratory tract disease Children are particularly susceptible Transmitted via respiratory droplets and person-to-person contact HPIV-1, 2, and 3 associated with lower respiratory infections HPIV-4 causes mild upper respiratory tract infections Croup Severe condition caused by HPIV-1 and HPIV-2 Characterized by inflammation of larynx, trachea, and bronchi Most patients recover from infection within two days No antiviral treatment available Intubation may be needed if airways become occluded

Enveloped, Unsegmented Negative ssRNA Viruses Mumps Mumps virus is the causative agent Transmission occurs via respiratory secretions Viruses infect upper respiratory system and spread to other organs Parotitis results Painful enlargement of the parotid salivary glands Orchitis, meningitis, pancreatitis, or deafness in one ear can occur Infection may also be asymptomatic Recovery is typically complete No specific treatment is available Vaccine has almost eradicated mumps in the industrialized world

Enveloped, Unsegmented Negative ssRNA Viruses Disease of Respiratory Syncytial Virus RSV causes a disease of the lower respiratory tract The virus causes syncytia formation in the lungs Infection can also result in difficult breathing known as dyspnea Leading cause of fatal respiratory disease in infants and children Infection is asymptomatic or a mild cold in older children and adults Immune response contributes to the damage to the lungs

Enveloped, Unsegmented Negative ssRNA Viruses Rabies Rabies virus is the causative agent Virus attaches to nerve cells and travels to central nervous system Infection causes spinal cord and brain degeneration Develop neurological manifestations characteristic of rabies Hydrophobia, seizures, disorientation, hallucination, and paralysis Death results from respiratory paralysis and other complications

Enveloped, Unsegmented Negative ssRNA Viruses Rabies Epidemiology of rabies Classical zoonotic disease of mammals Primary reservoir of rabies in urban areas is the dog Bats are the source of most cases of rabies in humans Transmission usually occurs via a bite Virus sometimes introduced through break in the skin or inhalation

Enveloped, Unsegmented Negative ssRNA Viruses Hemorrhagic Fevers Marburg virus and Ebola virus are the causative agents Natural reservoir and mode of transmission to humans unknown Spread person to person by contaminated body fluids and syringes Virions attack many cells of the body Especially macrophages and liver cells Uncontrolled bleeding under the skin and from every body opening Viral glycoprotein prevents neighboring cells from adhering Allows blood to leak out of the vessels Up to 90% of human victims die Symptoms are diagnostic The only treatment involves fluid replacement

Figure 25.33 Filamentous Ebola viruses. 52

Figure 25.35 Working in a Biosafety Level 4 lab. 53

Enveloped, Segmented Negative ssRNA Viruses Capsids contain segmented genome Orthomyxoviridae Flu viruses Bunyaviridae and Arenaviridae Hundreds of viruses that normally infect animals but can be transmitted to humans

Enveloped, Segmented Negative ssRNA Viruses Influenza Caused by orthomyxovirus types A and B Influenzaviruses rarely attack cells outside the lungs Genome consists of eight different ssRNA molecules Envelope studded with two glycoproteins important for attachment Neuraminidase (NA) Provides virus access to cell surface by hydrolyzing mucus in the lungs Hemagglutinin (HA) Attaches to pulmonary epithelial cells and triggers endocytosis

Enveloped, Segmented Negative ssRNA Viruses Influenza The genomes of flu viruses are highly variable Especially with respect to the genes that code for HA and NA Mutations result in production of new strains of influenzavirus Occurs via two processes Antigenic drift Antigenic shift Often occurs in Asia due to the dense population of humans and domesticated birds and pigs

Enveloped, Segmented Negative ssRNA Viruses Influenza Estimated a new pandemic could involve one-third of the world's population Viruses multiply in epithelial cells lining the lung Death of infected epithelial cells eliminate the lungs' epithelial lining Patients more susceptible to secondary bacterial infections Symptoms include fever, malaise, headache, and myalgia Induced by cytokines released as part of the immune response

Enveloped, Segmented Negative ssRNA Viruses Influenza Epidemiology of influenza Infection occurs primarily through inhalation of airborne viruses Strains are named by type, location and date of identification, and antigen Millions of infections occur in the U.S. each year Estimated that 64,000 die annually Individuals with weak immune systems are most vulnerable

Enveloped, Segmented Negative ssRNA Viruses Diseases of Bunyaviruses Most bunyaviruses are zoonotic pathogens Usually transmitted to humans by biting arthropods Have a segmented genome of three ssRNA molecules

Enveloped, Segmented Negative ssRNA Viruses Diseases of Bunyaviruses Epidemiology of bunyavirus infections Four genera contain human pathogens Cause disease throughout the world Arboviruses cause Rift Valley fever, California encephalitis, and hemorrhagic fevers Initial viremia spreads the virus to target organs Symptoms are usually mild Hantaviruses are not arboviruses Humans inhale virions in dried mouse urine or feces American strains cause hantavirus pulmonary syndrome Severe, often fatal pneumonia

Enveloped, Segmented Negative ssRNA Viruses Diseases of Arenaviruses Have a segmented genome of two ssRNA molecules Arenaviruses contain ribosomes Give them a sandy appearance in electron micrographs No evidence the viruses utilize them in nature

Enveloped, Segmented Negative ssRNA Viruses Diseases of Arenaviruses Zoonoses Hemorrhagic fevers (Lassa, Junin, Sabiá, Machupo) Endemic in rodent populations in Africa and South America Severe bleeding under the skin and into internal organs Lymphocytic choriomeningitis (LCM) Typically causes flulike symptoms Transmitted by aerosols, contaminated food, or from fomites Lassa fever virus can spread through contact with body fluids Diagnosis based on symptoms and immunoassays Supportive care is the primary treatment Prevention involves controlling and limiting contact with rodents

Enveloped, Segmented Negative ssRNA Viruses Diseases of Arenaviruses Hepatitis D Hepatitis D virus is the causative agent Transmitted through bodily fluids Via sexual activity and contaminated needles Hepatitis D virus requires hepatitis B virus to be virulent Hepatitis D virus can't attach to liver cells Hepatitis D plays a role in triggering liver cancer Precautions that limit spread of hepatitis B virus also prevent hepatitis D infection Vaccination against hepatitis B limits spread of hepatitis D viruses

Naked, Segmented dsRNA Viruses Reoviridae Respiratory and enteric viruses Have naked icosahedral capsids Only microbes with genomes composed of double-stranded RNA Originally considered respiratory enteric orphans (reo) Not initially associated with any diseases Include Rotavirus and Coltivirus

Naked, Segmented dsRNA Viruses Rotaviruses Capsid glycoproteins function similarly to enveloped viruses Act as attachment molecules and trigger endocytosis Most common cause of infantile gastroenteritis Significant cause of death in developing countries Transmitted via the fecal-oral route Infections are usually self-limited Treatment involves the replacement of water and electrolytes Prevention relies on good hygiene and proper sewage treatment A vaccine is available that provides some protection

Naked, Segmented dsRNA Viruses Coltiviruses Arbovirus Causes zoonotic disease called Colorado tick fever Infections usually produce mild disease involving fever and chills Severe cases can also occur with various manifestations The disease is usually self-limiting Infections diagnosed by immunoassay No specific treatment Prevention involves limiting contact with ticks

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