Chapter 25 Pathogenic RNA Viruses.

Chapter 25 Pathogenic RNA Viruses

RNA Viruses Only infective agents that store genetic information in RNA molecules RNA viruses are categorized by: 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)

RNA Viruses Positive RNA Acts like mRNA
Can be used by a ribosome to translate protein Negative RNA Must first be transcribed as mRNA to be processed by a ribosome

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

Common Colds Caused by Rhinoviruses Cause most cases of the common cold Infections limited to the upper respiratory tract A single virus is often sufficient to cause a cold Virus transmitted by aerosols, by fomites, or via hand-to-hand contact Most commonly transmitted by direct person-to-person contact Some immunity can be acquired against serotypes infected with in the past The number of infections tends to decrease with age

Rhinoviruses, the most common cause of colds
Figure 25.1

Common Colds Caused by Rhinoviruses Manifestations of rhinoviruses are usually characteristic Medications can help relieve the symptoms Do not reduce the duration of the disease Handwashing is the most important preventative measure

Diseases of the Enteroviruses Transmitted via the fecal-oral route or respiratory secretions Ingestion of contaminated food or water Via fomites Oral contact with infected hands or fomites Infect the pharynx and intestine Spread via the blood infecting various targets in the body Three main enteroviruses Polioviruses, coxsackieviruses, and echoviruses

Diseases of the Enteroviruses Poliomyelitis Polio is caused by one of three serotypes of poliovirus can eventually get to CNS Four conditions caused by polioviruses Asymptomatic infections Minor polio Nonparalytic polio Paralytic polio Can result in bulbar poliomyelitis limb and/or respiratory paralysis

A hospital ward full of mechanical respirators
Figure 25.2

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

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

Diseases of the Enteroviruses Other diseases of enteroviruses Coxsackie A viruses Produce lesion and fever Herpangina Hand-foot-and-mouth disease Coxsackie B viruses Associated with myocarditis and pericardial infections Can be transmitted across the placenta Echoviruses Acquired intestinally and can cause meningitis and colds

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

Diseases of the Enteroviruses Diagnosis, treatment, and prevention Enterovirus infections usually have mild symptoms Not diagnosed except in severe cases No antiviral therapy is effective Good hygiene and adequate sewage can prevent infections Effective vaccines are available for hepatitis A and polio

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 Infection does not cause chronic liver disease Complete recovery occurs most of the time

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 Astroviruses cause diarrhea but no vomiting No specific treatment except replacement of fluid and electrolytes

Viruses of the families Caliciviridae and Astroviridae
Figure 25.6

Hepatitis E Also known as enteric hepatitis Caused by hepatitis E virus Formerly classified as a calicivirus Fatal in 20% of pregnant women No treatment Prevent by interrupting the fecal-oral route of transmission

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

Diseases of Positive 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 Most infections result in mild, flu-like symptoms Arboviruses can occasionally result in second-stage infections Encephalitis, dengue fever, and yellow fever

Hosts and transmission of viruses of WEE and EEE
Figure 25.9

Aedes aegypti mosquito
Figure 25.11

Pathogenesis of dengue hemorrhagic fever
Figure 25.12

Diseases of Positive RNA Arboviruses Serological tests often used for diagnosis of arbovirus infections Supportive care is the only treatment Vaccines exist for some of the arboviruses Recommended for people traveling to areas where arboviral diseases are prevalent

Zika Virus transmitted by Aedes mosquitoes (same as Dengue)
mother to child (adverse effects still being studied) blood transfusion not known- no confirmed cases yet, but found in blood in donors sexually (usually men) Causes- fever, rash, joint pain, conjuctivitis illness usually mild- rarely causes death History: has been found in Africa, Asia, and Pacific Islands

Other Diseases of Enveloped +ssRNA Viruses Rubella Also called “German measles” Rubella virus is the causative agent 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

The rash of rubella Figure 25.13

The efficacy of vaccination against rubella
Figure 25.14

Hepatitis C virus (HCV) transmitted parenterally by exposure to blood and blood products IV drug users and organ transplant recipient are at high risk Sexual and maternal-fecal routs of transmission less common HCV-associated cirrhosis is the most common indication for liver transplant Primary infection asymptomatic or mild illness, nonspecific symptoms Chronic hepatitis develops in 75% of infection and MAY progress to liver cirrhosis with elevated risk for hepatocellular carcinoma Diagnosed most common detection of anti HCV antibodies and PCR No vaccine available Chronic HCV is treated with interferon alpha and ribavirin

Comparison of Hepatitis Viruses
Figure 25.3

Other Diseases of Enveloped +ssRNA Viruses Diseases of coronaviruses Named due to 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 No treatment or vaccine is available

Coronaviruses Figure 25.15

Prevention of SARS Figure 25.16

Enveloped +ssRNA coronavirus
Figure 25.8

Enveloped, Positive ssRNA Viruses with Reverse Transcriptase
Retroviridae 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

Reverse transcriptase
Figure 25.17

Acquired Immunodeficiency Syndrome AIDS is not a disease but a syndrome AID Syndrome Certain opportunistic or rare infections that occur in the presence of antibodies against HIV and a CD4 white blood cell count below 200 cells/microliter of blood HIV Likely arose from mutation of simian immunodeficiency virus Only replicates in humans Destroys the human immune system

Characteristics of HIV that challenge the immune system
Figure 25.6

Acquired Immunodeficiency Syndrome Two major types of HIV HIV-1 is prevalent in the United States and Europe HIV-2 is prevalent in West Africa Glycoproteins gp120 and gp41 impede immune clearance of HIV gp120 exhibits antigenic variability gp41 promotes fusion of the viral envelope to target cell

The replication cycle of HIV
Figure 25.19

Process by which HIV attaches to and enters a CD-4 cell
Figure 25.20

The course of AIDS Figure 25.21

Diseases associated with AIDS
Figure 25.22

Acquired Immunodeficiency Syndrome Epidemiology of AIDS AIDS first recognized in young male homosexuals in the U.S. AIDS is now found throughout the world HIV found in blood, semen, saliva, vaginal secretions, and breast milk Blood and semen more infective than other secretions Infected fluid must contact a tear or lesion in the skin or mucous membranes Infected fluids can also be injected into the body

Modes of HIV transmission in Americans during 2007
Figure 25.24

Acquired Immunodeficiency Syndrome Diagnosis Serological diagnosis involves detecting antibodies against HIV Positive test does not indicate presence of AIDS Signs and symptoms vary according to the diseases present Long-term nonprogressors appear not to develop AIDS May be due to defective virions or lack of effective coreceptors for the virus

Acquired Immunodeficiency Syndrome Treatment HAART currently used to reduce viral replication Cocktail of antiviral drugs Various problems must be overcome to develop vaccine Prevention Behavioral changes can slow progression of AIDS epidemics Abstinence and safe sex Use of clean needles Screening of blood products Administering AZT to infected pregnant women

Enveloped, Unsegmented Negative ssRNA Viruses
Paramyxoviridae Cause cells to fuse and form giant, multinucleate syncytia Syncytia enable the virus to evade the immune system Four genera infect humans Morbillivirus (measles virus) Paramyxovirus (parainfluenza virus) Rubulavirus (mumps virus) Pneumovirus (respiratory syncytial virus)

A syncytium formed by paramyxoviruses
Figure 25.25

Measles One of five classical childhood diseases Spread in the air via respiratory droplets Viral spread requires large, dense populations of people infection rate of 85-95% Viruses infect the respiratory tract then spread throughout the body Koplik’s spots appear on the mucous membrane (buccal mucosa)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)

Signs of measles Figure 25.26

Measles Signs of measles, particularly Koplik’s spots, are diagnostic No antiviral treatment is available Vaccine has eliminated endemic measles in the United States live attenuated vaccine (MMR) Measles remain a frequent cause of death in other countries

Number of cases of measles in the United States since 1950
Figure 25.27

Diseases of Parainfluenza Virus (PIV) Cause respiratory tract disease Children are particularly susceptible Croup Caused by parainfluenza viruses 1 and 2 Characterized by inflammation of larynx, trachea, and bronchi fever, hoarseness, a barking cough and inspiratory stridor Transmitted via respiratory droplets and person-to-person contact or fomites Most patients recover from infection within two days No specific treatment or vaccines for PIV

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 Infection is often asymptomatic Recovery is typically complete No specific treatment is available Vaccine has almost eradicated mumps in the industrialized world

Parotitis Figure 25.28

Incidence of mumps in the United States
Figure 25.29

Disease of Respiratory Syncytial Virus (RSV) Disease limited to the respiratory tract Transmission occurs via fomites, hands, and respiratory droplets The virus causes syncytia formation in the lungs Infection can also result in difficult breathing known as dyspnea Most common cause of bronchiolitis and pneumonia in infants and children -cough, wheezing and cyanosis

Disease of Respiratory Syncytial Virus (RSV) Leading cause of fatal respiratory disease in infants and children Infection is asymptomatic or a mild cold in older children and adults Diagnosis based on the signs of respiratory distress Verified by immunoassay isolation in cell culture Treatment is supportive ribavirin aerosol is approved for treatment of infants with severe RSV infection

Rhabdoviridae Include a variety of plant and animal pathogens Rabies is the most significant pathogen Filoviridae Cause a number of emerging diseases Include Ebola and Marburg hemorrhagic fevers

Rabies Rabies virus is the causative agent 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 Virus attaches to nerve cells and travels to central nervous system Rabies-specific neurological manifestations (e.g., hydrophobia) Death results from respiratory paralysis and other complications

A rabies virus Figure 25.30

Predominant wildlife reservoirs for rabies
Figure 25.31

Rabies Diagnosis Neurological symptoms of rabies are usually sufficient Too late to intervene by the time symptoms and antibodies occur Treatment Treatment of the site of infection Injection of human rabies immune globulin Vaccination with human diploid cell vaccine (HDCV) Prevention Vaccination of domestic dogs and cats can help control rabies

Negri bodies, a characteristic of rabies infection
Figure 25.32

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 The only treatment involves fluid replacement Up to 90% of human victims die

Filamentous Ebola viruses
Figure 25.33

Sites of known human cases of Marburg and Ebola virus
Figure 25.34

Laboratory personnel working in level four biocontainment
Figure 25.35

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

Influenza Caused by orthomyxovirus types A and B Infection occurs primarily through inhalation of airborne viruses Rarely attack cells outside the lungs 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

Influenzaviruses Figure 25.37

Influenza The genomes of flu viruses are highly variable Especially with respect to the envelope components Hemagglutinin (HA) Neuraminadase (NA) Mutations result in production of new strains of influenzavirus Occurs via two processes Antigenic drift Antigenic shift

The development of new strains of flu viruses
Figure 25.38

Influenza Diagnosis Signs and symptoms during community-wide outbreak Treatment Drugs prevent viral uncoating or block virion release from infected cells Must be administered within first 48 h of infection Prevention Immunization with multivalent vaccines Protective only against the strains included in the vaccine

Emerging (and Reemerging) Viruses
An emerging disease is one that has appeared in a population for the first time, or that may have existed previously but is rapidly increasing in incidence or geographic range. World Health Organization (WHO) Many have RNA genomes rapidly changing (quasispecies) Major threat to human and veterinary public health Factors that influence climate change destruction of rain forests increased international travel

Examples of Emerging and Reemerging Viruses
Influenza MERS-CoA HIV West Nile Viruses Polioviruses

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