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Chapter 25

Pathogenic RNA Viruses

RNA Viruses

•   RNA viruses are the only infective agents that use RNA molecules to store their genetic information

•   RNA viruses are categorized by their genomic structure, the presence of an envelope, and the size and shape of their capsid

Includes:

Positive single-stranded RNA (+ssRNA) viruses

•Picornaviridae, Caliciviridae, Astroviridae, Togaviridae, Flaviviridae, and Coronaviridae

•Retroviruses (+ssRNA viruses that convert their genome to DNA inside a cell)

•Negative single-stranded RNA (-ssRNA) viruses

•Paramyxoviridae, Rhabdoviridae, Filoviridae, Orthomyxoviridae, Bunyaviridae, and Arenaviridae

 

 

Picornaviridae, Caliciviridae, and Astroviridae families

•   Picornaviruses

•   Smallest of the animal viruses

•   Picornaviruses that cause disease are in two genera

•   Rhinovirus and Enterovirus

•   Caliciviruses and astroviruses

•   Larger than picornaviruses

•   Cause gastrointestinal disease

 

Rhinovirus

•   Cause most cases of the common cold

•   Infections are limited to the upper respiratory tract

•   A single virus is often sufficient to cause a cold

•   The virus can be spread through aerosols, via fomites, or via hand-to-hand contact

•   Direct person-to-person contact is the most common means of transmission

•   Individuals can acquire some immunity against serotypes that have infected them in the past

•   As a result, the number of infections tends to decrease with age

Diagnosis, Treatment, and Prevention

•   Diagnosis

•   Manifestations of rhinoviruses are usually characteristic

•   Treatment

•   Medications can help relieve the symptoms but they do not reduce the duration of the disease

•   Rest and fluids aid in mounting an effective immune response

•   Prevention

•   Handwashing is the most important preventative measure

Enteroviruses

•   So named because they are transmitted via the fecal-oral route

•   Infection usually involves ingestion of contaminated food or water or oral contact with infected hands or fomites

•   Infect the pharynx and intestine but can spread and infect various targets in the body

•   4 main enteroviruses

•   Polioviruses, hepatitis A virus, coxsackieviruses, and echoviruses

Poliomyelitis

•   Polio is caused by one of three serotypes of poliovirus

•   Wild-type poliomyelitis has not occurred in the Americas since 1979

•   4 conditions caused by polioviruses

•   Asymptomatic infections result most of the time

•   Minor polio which produces nonspecific symptoms

•   Nonparalytic polio can result from invasion of the meninges and central nervous system

•   Paralytic polio results from the invasion of the spinal cord and the brain

•   Bulbar poliomyelitis can result in paralysis of respiratory muscles requiring the use of iron lungs to assist respiration

•   Postpolio syndrome results in a crippling deterioration in the function of polio-affected muscles

•   The near elimination of polio is due to the development of two effective vaccines

Hepatitis A

•   Hepatitis A virus is the causative agent

•   Hepatitis A can survive on various surfaces and is resistant to common household disinfectants

•   Transmitted through the fecal-oral route

•   The signs and symptoms are the result of the patient’s immune response

•   Infection does not cause chronic liver disease

•   Complete recovery occurs most of the time

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

•   Coxsackie A viruses

•   Produces lesion and fever

•   Herpangina are lesions of the mouth and pharynx that resemble herpes lesions

•   Hand-foot-and-mouth disease involves lesions on the extremities and in the mouth

•   Coxsackie B viruses

•   Associated with myocarditis and pericardial infections

•   Can be transmitted across the placenta

•   Coxsackie A and B viruses can cause viral meningitis

•   Echoviruses

•   These viruses are acquired intestinally and can cause meningitis and colds

Diagnosis, Treatment, and Prevention

•   Enterovirus infections usually have mild symptoms and are 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

Acute Gastroenteritis and Hepatitis E

•   Caliciviruses and astroviruses can cause acute gastroenteritis

•          Can cause outbreaks in daycare centers, schools, and hospitals

•   Caliciviruses cause diarrhea, nausea, and vomiting

•   Astroviruses cause diarrhea but no vomiting

•   Hepatitis E virus was formerly classified as a calicivirus

•   Causes hepatitis E which is also known as enteric hepatitis

the Togaviridae, Flaviviridae, and Coronaviridae families

•   Togaviridae and Flaviviridae

•   Enveloped, icosahedral, +ssRNA viruses

•   Designated arboviruses because they are often transmitted by arthropods

•   Coronaviridae

•   Enveloped, helical, +ssRNA viruses

Diseases of Positive RNA Arboviruses

•   Mosquitoes and ticks transmit the arboviruses among animal hosts

•   Diseases spread from animal reservoirs to humans are zoonoses

•   Arthropod vectors remain infected and 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, West Nile and yellow fever

Diagnosis, Treatment, and Prevention

•   Hemagglutination inhibition, ELISA, and agglutination assays are often used for diagnosis of arbovirus infections

•   Supportive care is the only treatment

•   Vaccines exist for some of the arboviruses

 

Rubella

•   Also called “German measles’

•   Rubella virus is the causative agent

•   One of the five childhood diseases that produces skin lesions

•   Infection begins in the 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

•   Rubella infections of pregnant women can result in congenital defects or death of the child

•   Vaccination has been effective at reducing the incidence of rubella

Hepatitis C

•   Caused by the a flavivirus called hepatitis C virus (HCV)

•   Accounts for most of the non-A, non-B hepatitis in the Unites States

•   HCV is spread through needles, organ transplants, and sexual activity

•   Hepatitis C is a chronic infection with few if any symptoms

•   Severe liver damage and liver failure can occur over time

•   No treatment or vaccine for hepatitis C

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

•   Can cause gastroenteritis in children

•   Diseases are mild

•   No treatment or vaccine is available

Retroviridae

•   Studied more than any other group of viruses

•   Have polyhedral capsids with spiked envelopes

•   Retroviruses transcribe dsDNA from ssRNA using reverse transcriptase

•   Two types of retroviruses

•   Viruses that are primarily oncogenic

•   Viruses that are primarily immunosuppressive

Oncogenic Retroviruses

•   Human T-lymphotrophic virus 1 (HTLV-1)

•   First identified in a patient with adult acute T-cell lymphocytic leukemia

•   HTLV-2

•   Causes a rare cancer called hairy-cell leukemia

•   HTLV-1 and HTLV-2 are transmitted via sexual intercourse, blood transfusion, and contaminated needles

Oncogenic Retroviruses

•   Infections are chronic and long-term prognosis of patients is poor

•   Exact way oncogenic retroviruses cause cancer is unclear

Acquired Immunodeficiency Syndrome

•   AIDS is not a disease but a syndrome

•   AID syndrome is any of certain opportunistic or rare infections that occur in the presence of antibodies against the human immunodeficiency virus (HIV)

•   HIV

•   Likely arose from mutation of the simian immunodeficiency virus (SIV), found in African monkeys

•   HIV only replicates in humans and destroys the human immune system

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

•   The glycoproteins gp120 and gp41 impede the immune clearance of HIV because of antigenic variability (gp120) and the ability to fuse with host cells (gp41)

•   HIV replication cycle is similar to other animal retroviruses

 

Epidemiology of HIV

•   AIDS was first recognized in young male homosexuals in the United States

•   AIDS is now found throughout the world

•   HIV is found in sufficient concentrations to cause infection in blood, semen, saliva, vaginal secretions, and breast milk

•   Blood and semen are more infective than other secretions

•   Infected fluid must come in contact with a tear or lesion in the skin or mucous membranes or be injected into the body

•   HIV is transmitted primarily via sexual contact and intravenous drug use

•   HIV is also transmitted from mother to baby across the placenta and in breast milk

•   Certain behaviors increase the risk of infection

•   Sexual promiscuity

•   Anal intercourse

•   Intravenous drug use

•   Sexual intercourse with anyone in the previous three categories

Diagnosis, Treatment, and Prevention

•    Diagnosis

•   Serological diagnosis involves detecting antibodies against HIV

•   A positive test indicates infection with HIV but not the presence of AIDS

•   Signs and symptoms of AIDS 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

•   Treatment

•   A “cocktail” of several antiviral drugs is currently used

•   Cocktails reduce viral replication but do not cure the infection

•   Vaccine development is difficult because various problems must be overcome

•   Prevention

•   Behavioral changes can help slow the progression of AIDS epidemics

•   Includes abstinence and safe sex, use of clean needles, screening of blood products, and administering AZT to infected pregnant women

Paramyxoviridae, Rhabdoviridae, and Filoviridae families

•   Paramyxoviridae

•   Have the ability to cause infected cells to fuse with neighboring cells and form giant, multinucleate syncytia

•   Syncytia enable the virus to pass into neighboring cells and evade the immune system

•   Four genera infect humans

•   Morbillivirus (measles virus), Paramyxovirus (parainfluenza), Rubulavirus (mumps virus), and Pneumovirus (respiratory syncytial virus)

Paramyxoviridae, Rhabdoviridae, and Filoviridae families

•   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

Measles(Morbillivirus)

•   One of five classical childhood diseases

•   Spread in the air via respiratory droplets

•   Viral spread requires large, dense populations of people

•   Viruses infect the respiratory tract and then spread throughout the body

•   Characteristic lesions called 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

•   Include pneumonia, encephalitis and subacute sclerosing panencephalitis (SSPE)

Diagnosis, Treatment, and Prevention

•   Signs of measles, particularly Koplik’s spots, are diagnostic for the disease

•   No antiviral treatment is available

•   The live, attenuated vaccine has eliminated measles as an endemic disease in the United States

•   Measles remain a frequent case of death in other countries

Parainfluneza Virus

•   Cause respiratory tract disease

•   Children are particularly susceptible

•   Transmission occurs via respiratory droplets and person-to-person contact

•   Infection with influenza viruses 1 and 2 can result in croup

•   Most patients recover from infection within 2 days

Mumps (Rabulavirus)

•   Mumps virus is the causative agent

•   Transmission occurs via respiratory secretions

•   Viruses infect the upper respiratory system and then spread to other organs

•   The parotid glands are particularly susceptible and become painfully enlarged

•   Infection is often asymptomatic though other conditions can occur

•   Recovery is typically complete

•   No specific treatment is available

•   Mumps has almost been eradicated in the industrialized world because humans are the only natural host and an effective vaccine is available

Respiratory Syncytial Virus

•   Causes a disease limited to the respiratory tract

•   Transmission occurs via fomites, hands, and sometimes respiratory droplets

•   The virus causes syncytia formation in the lungs

•   Infection can also result in dyspnea, or difficulty breathing

•   Is the leading cause of fatal respiratory disease in infants and children worldwide

•   Infection is asymptomatic or a mild cold in older children and adults

Diagnosis, Treatment, and Prevention

•   Diagnosis is based on the signs of respiratory distress verified by immunoassay

•   Treatment is supportive

•   Ribavirin is used to treat extreme cases

Rabies (Rhabdovirus)

•   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 though a break in the skin or inhalation can sometimes introduce the virus into the body

•   The virus attach to skeletal muscle cells then travel to the central nervous system

Rabies

•   When the virus infects the central nervous system neurological manifestations specific to rabies develop (such as hydrophobia)

•   Death results from respiratory paralysis and other neurological complications

Diagnosis, Treatment, and Prevention

•   Diagnosis

•   Neurological symptoms of rabies are unique and usually sufficient

•   By the time symptoms and antibodies occur it is too late to intervene

•   Treatment

•   Treatment of the site of infection

•   Injection of human rabies immune globulin

•   Vaccination with human diploid cell vaccine (HDCV)

•   Viral replication and movement to the brain is slow enough to allow effective immunity to develop before disease develops

•   Prevention

•   Vaccination of domestic dogs and cats can help control rabies

•   Little can be done to eliminate rabies in wild animals

Hemorrhagic Fevers (Filovirus)

•   Marburg virus and Ebola virus are the causative agents

•   The natural reservoir and mode of transmission to humans are unknown

•   Spread from person to person via contaminated bodily fluids, primarily blood, and contaminated syringes

•   The virions attack many cells of the body, especially macrophages and liver cells

•   Infections results in uncontrolled bleeding under the skin and from every body opening

•   Due to a viral glycoprotein that prevents neighboring cells from adhering which allows blood to leak out of the vessels

•   The only treatment involves fluid replacement

•   Up to 90% of human victims die

Orthomyxoviridae, Bunyaviridae, and Arenaviridae families

•   Orthomyxoviridae

•   Flu viruses

•   Bunyaviridae, and Arenaviridae

•   Include hundreds of viruses that normally infect animals but can be transmitted to humans

Influenza

•   Caused by two species of orthomyxovirus, designated types A and B

•   Infection occurs primarily through inhalation of airborne viruses

•   Rarely attack cells outside the lungs

•   Death of the epithelial cells infected with influenza viruses eliminate the lungs first line of defense against infections, the epithelial lining

•   Flu patients become more susceptible to secondary bacterial infections

•   Symptoms include fever, malaise, headache, and myalgia

•   Induced by cytokines released as part of the immune response

•   The genomes of flu viruses are highly variable, especially with respect to the envelope components, hemagglutinin (HA) and neuraminadase (NA)

•   The changing antigens guarantee that there will be susceptible people

 

 

Diagnosis, Treatment, and Prevention

•   Diagnosis

•   Manifestations of flu signs and symptoms during a community-wide outbreak of the flu is often sufficient

•   Treatment

•   Drugs are available that prevent uncoating of the virus or block release of virions from infected cells

•   Must be administered early because they don’t prevent the later manifestations of the disease

•   Prevention

•   Immunization with multivalent vaccines

•   Contain several antigens within a single vaccine

•   Protective only against the strains included in the vaccine

Diseases of Bunyaviruses

•   Most bunyaviruses are zoonotic pathogens

•   Usually transmitted to humans by biting arthropods

•   Infections result with an initial viremia spreading the virus to target organs

•   Symptoms are usually mild

•   Hantviruses are the exception

•   Transmitted to humans via inhalation of virions in dried deer-mouse urine or feces

•   American strains can cause a rapid, severe, and often fatal pneumonia called hantavirus pulmonary syndrome

Diseases of Arenaviruses

•   Arenaviruses contain ribosomes that give them a sandy appearance in electron micrographs

•   Can cause zoonotic diseases and hepatitis D

Zoonoses

•   Zoonotic diseases include hemorrhagic fevers and lymphocytic choriomeningitis (LCM)

•   Hemorrhagic fevers

•   Includes Lassa and Junin hemorrhagic fevers

•   Cause severe bleeding under the skin and into internal organs

•   LCM

•   Typically causes flu-like symptoms

•   Transmission occurs through the inhalation of aerosols or consumption of contaminated food, or from fomites

•   Lassa fever virus can be spread through contact with bodily fluids

Hepatitis D

•   Hepatitis D virus is the causative agent

•   Transmission occurs through bodily fluids via sexual activity and contaminated needles

•   Hepatitis D virus requires hepatitis B virus to become virulent

•   Hepatitis D virus doesn’t posses the glycoproteins needed to attach to liver cells and must “steal” them from a hepatitis B virus infecting the same cell

•   Hepatitis D may play a role along with hepatitis B virus in triggering liver cancer

•   Vaccination with the hepatitis B vaccine limits the spread of hepatitis D viruses

dsRNA Viruses

•   Includes only the Reoviridae family

•   Reoviruses are the only microbes with genomes composed of double-stranded RNA

•   Termed respiratory enteric orphans because they are respiratory and enteric viruses that were not initially associated with any diseases

•   Include the Rotaviruses and Coltiviruses

Reoviruses

•   Cause infantile gastroenteritis

•   Account for approximately 50% of all cases of diarrhea in children requiring hospitalization as a result of fluid and electrolyte loss

•   Transmitted via the fecal-oral route

•   Infections are usually self-limited

•   Treatment involves the replacement of water and electrolytes

•   A vaccine is available that provides some protection but has been linked to a rare bowel blockage condition in some children

Coltiviruses

•   Arbovirus that causes a zoonotic disease called Colorado tick fever

•   Infections usually result in a mild disease involving fever and chills

•   Severe cases can also occur with various manifestations

•   The disease is usually self-limiting

 

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