P1: V. MEDICALLY IMPORTANT RNA VIRUSES

unti flaviviridae only

In the provirus stage, the genome is transcribed into ____ by host ____.

mRNA ; RNA polymerase

• The retroviruses have an icosahedral-shaped, enveloped virion.

• They range in size from 80 to 130 nm

Retrovirus

• Retroviruses contain an ______ for replication.

• Reverse transcriptase uses _____ as a template to make double-stranded DNA that then moves into the ____where it is integrated into the ______.

• This stage is referred to as a ____

• RNA-dependent DNA polymerase (reverse transcriptase)

• viral RNA

• nucleus ; host chromosome

• provirus.

The human immunodeficiency virus 1 (HIV-1) and HIV-2 are members of the genus

Lentivirus

• HIV is the causative agent of ____.

• _____ causes a more severe infection and is much more prevalent than ____.

• AIDS

• HIV-1 ; HIV-2

HIV

• The virus initially infects ____ and ____, then the host’s ______.

• ____ is the primary receptor for the virus

• Important coreceptors include _____ and ____.

• macrophages ; dendritic cells ; CD4-positive T cells

• CD4

• CXCR4 ; CCR5

• Often mild and can resemble infectious mononucleosis.

• This stage of HIV infection occurs 3 to 6 weeks after infection, and antibodies are generally undetectable

• The virus exhibits high level of replication

• Rarely diagnosed 

Acute infection (acute retroviral syndrome)

In HIV ____ is present before antibodies can be detected.

p24

______ in serum can sometimes be detected in amplification assays as can p24

Viral RNA

• Virus replication occurs at a high rate in ____, but the patient remains asymptomatic for many years.

• The host can replace infected T cells as fast as they are destroyed 

• This condition is referred to as _____.

• lymphoid tissue

• clinical latency 

• As immune function is compromised, the patient presents with chronic and recurrent infections, including Pneumocystis pneumonia, CMV infections, mycobacteriosis, cryptosporidosis, candidiasis, and toxoplasmosis.

• This stage is sometimes referred to as ____

• AIDS-related complex

HIV has also been associated with malignant conditions such as ____ and _____.

Kaposi sarcoma ; B-cell lymphomas

• The Centers for Disease Control and Prevention (CDC) recommends that patients be screened with an

HIV-1/HIV-2 antibody p24 antigen combination test

• Samples that are negative or indeterminate in the differentiating tests should be tested with an _____

• FDA-approved HIV-1 NAAT.

HTLV-1 has been linked to ______ and _____

adult T-cell leukemia ; HTLV-1-associated myelopathy/tropical spastic paraparesis (HAM/TSP)

• Contain a segmented RNA genome and have a helical shaped virion with an envelope.

• They range in size from 75 to 125 nm

Orthomyxoviruses

Are the only members of the family Orthomyxoviridae

nfluenza viruses, A, B, and C,

• Orthomyxoviruses have ____ and _____ on their surface.

• These molecules are immunogenic, and antibodies to these molecules confer protection.

hemagglutinin (HA) and neuraminidase (NA)

• ______ allow the viruses to attach to the surface of respiratory epithelial cells and also agglutinate red blood cells.

• ____ has enzymatic activity, cleaving budding viruses from infected cells.

hemagglutinin (HA) and neuraminidase (NA)

• Develops when point mutations occur in the viral genes encoding the HA and NA spikes.

• Can occur within any of the three influenza viruses.

Antigenic drift

• Occurs following a major change (reassortment) of the RNA genome when a single host cell is infected with two different influenza viruses.

• Among the influenza viruses, it only occurs in influenza A viruses.

Antigenic shift 

• _____ vaccines are available; each year the formulation of the seasonal influenza vaccine can vary as the CDC tries to predict which influenza strains will predominate in the upcoming flu season.

Influenza trivalent and quadrivalent vaccines

In Influenza

• A number of rapid diagnostic influenza tests are commercially available.

• Results are available in about _____.

• The assays utilize an upper respiratory sample like a _____ or ____ and are based on direct ____ detection.

• NAATs are also available and take ___ hours

• 15 minutes

• nasopharyngeal swab ; throat swab ; antigen

• 1 to 8

• Cause childhood croup, which is a respiratory infection characterized by fever and a hoarse cough

• Diagnosis is based on clinical symptoms and confirmed by direct antigen detection of NAATs.

Parainfluenza viruses

• An infection of the parotid glands, causing swelling and difficulty in swallowing

• Rare in developed countries because of widespread use of a vaccine

• Diagnosis is generally made clinically

Mumps

• Necrotic vesicles with a white center surrounded by erythema on the oral mucosa, referred to as Koplik spots

• Vaccination programs have nearly eliminated measles in developed countries.

• Still relatively common in some developing countries, particularly in Africa and Asia.

Morbillivirus

• Causes respiratory and ear infections that are most common in newborns and young children.

• Worldwide, it is the most common cause of bronchitis and pneumonia in infants and children

Respiratory syncytial virus (RSV)

• Characterized by the formation of giant multinucleated cells

• Best made with real-time reverse transcriptase-PCR.

• Direct antigen detection is highly sensitive in children but not in adults.

Respiratory syncytial virus (RSV)

The family Paramyxoviridae contains

1. paramyxoviruses

2. morbilliviruses

3. pneumoviruses

4. megamyxoviruses.

Members of the genus Enterovirus

1. poliovirus

2. coxsackie viruses

3. echoviruses

Enteroviruses most commonly produce an

acute nonspecific febrile syndrome

Diagnosis is generally made by NAATs of clinical specimens: serum, CSF, throat swabs, rectal swabs, etc.

Enteroviruses

• Have a naked virion ranging in size from 20 to 30 nm

Picornaviruses

• Transmitted by the fecal-oral route.

• The virus initially infects the gastrointestinal tract but spreads to the CNS.

• Most infections are mild but can result in ____ or ___.

Poliovirus ;  meningitis or paralytic polio

• Cause hand, foot, and mouth disease of humans; this is not the same disease as foot and mouth disease of animals.

• Also associated with conjunctivitis.

Coxsackie virus

• Cause about one-third of all cases of myocarditis.

• They are also associated with meningitis.

Coxsackie B

• A frequent cause of the common cold.

• Grow better at temperatures just below core body temperature (e.g., 33°C)

• Over 100 serotypes are known, and immunity to one does not provide immunity to the others.

Rhinoviruses

• Have a double-stranded RNA genome.

• The virion is about 70 nm in diameter and has a wheel-like (spokes) appearance.

• Belong to the family Reoviridae.

Rotaviruse

• The the most important cause of gastrointestinal infections in children less than 2 years of age.

• Severe diarrhea and dehydration are common in this age group.

• Two oral vaccines are available and recommended beginning at 2 months of age.

Rotaviruses

• Diagnosis: Antigen detection via latex agglutination or ELISA and, less commonly, immunoelectron microscopy

Rotaviruse

• Cause colds, lower respiratory tract infections, and gastrointestinal tract infections in humans and other animals.

• Diagnosis is generally made by detecting antibodies in serum.

Coronaviridae

The family Caliciviridae contains four genera:

1. Norovirus

2. Sapovirus

3. Lagovirus

4. Vesivirus

Calciviridae

•  The ____  and _____ (members of the genus Norovirus) are highly contagious and are important causes of gastroenteritis.

• noroviruses and Norwalk viruses

The virions are about 70 nm in diameter and contain an envelope and has two genera

Togaviridae

• The virus causes a mild infection.

• However, it can produce severe congenital infections if women are infected in the early stage of pregnancy; therefore, pregnant women and women of childbearing age are often tested for immunity.

Rubivirus: Rubella virus

• This genus contains about 25 viruses, all of which are transmitted by arthropods

• Can produce generalized symptoms of fever, malaise, headache, and/or symptoms of encephalitis

Alphavirus

Many viruses belonging to the family Flaviviridae are _____

arboviruses

• First reported in the United States in 1999 in New York

• Typically produces mild or asymptomatic infections in many individuals

  who are otherwise healthy.

• However, the most serious complication is fatal encephalitis (inflammation of the brain).

• People over the age of 60 years are most susceptible to encephalitis.

West Nile virus

• Laboratory diagnosis of the infection can be made by detecting antibodies to the virus in serum or CSF.

• ELISA antigen capture and RT-PCR assays are also available.

West Nile virus

• Has been reported in Africa, Central and South America, and the southern United States.

• Transmitted by mosquitoes, sexual contact, and to a fetus during pregnancy

• Infections acquired in utero can result in microcephaly and other severe fetal brain defects.

Zika virus

• _____ is important in diagnosing Zika virus infection

• _____ can be performed following an amniocentesis to diagnose in utero

  infections.

• Travel history

• RT-PCR

• Four serologically distinct viruses cause the tropical disease

• An estimated 400 million people are infected yearly.

• Mosquitoes are the vectors.

Dengue virus

• The signs and symptoms of dengue are variable but generally include a high fever along with other symptoms such as severe headache, joint pain, muscle and/or bone pain, low white blood cell count, and mild bleeding problem

• Diagnosis is based on travel history, clinical presentation, serologic assays, and molecular test

Dengue virus

• A severe form of dengue is known as _____.

• dengue hemorrhagic fever

• Another tropical disease transmitted by mosquitoes.

• The disease is rare in the United States.

• A vaccine is available.

• Most people infected are asymptomatic or have mild symptom

Yellow fever virus