RNA Viruses

Virology II: Advanced Medical Microbiology & Immunology

RNA Viruses

RNA Viral Pathogens

  • Types of RNA viruses classified by their genome structure:

    • Positive-sense (+), single-stranded (ss) RNA viruses

    • Picornaviruses: Includes Enteroviruses, Rhinoviruses

    • Calciviruses: Norovirus

    • Flaviviruses: Yellow Fever, Dengue, St. Louis Encephalitis, Hepatitis C, West Nile

    • Togaviruses: Rubella

    • Coronaviruses: SARS, COVID-19

    • Negative-sense (-), Single-Stranded, Linear RNA Viruses (All Enveloped)

    • Orthomyxoviruses (segmented x8): Influenza A & B

    • Paramyxoviruses: Measles, Mumps, RSV, PIV

    • Rhabdoviruses: VSV, Rabies

    • Filoviruses: Ebola, Marburg

    • Arenaviruses (segmented x2): LCMV, Lassa

    • Bunyaviruses (segmented x3): Sin Nombre virus, Hantavirus

Calciviridae

  • Characteristics

    • Naked, icosahedral structure

    • Positive-sense ssRNA: Norovirus

  • Transmission

    • Via fecal-oral route, contaminated food, and water

  • Epidemiology

    • Outbreaks can occur year-round in developed countries

    • Resistant to desiccation and chlorine

  • Clinical Manifestation

    • Causes acute gastroenteritis, contributing to 60% of all non-bacterial gastroenteritis in the US

    • Symptoms include nausea, vomiting, and watery diarrhea

    • Incubation period: 24-48 hours; illness resolves in 12-60 hours

    • Immunity after infection is short-lived

Picornaviridae

  • Characteristics

    • Small, naked, icosahedral viruses

  • Replication & Transmission

    • Virus replicates in the cytoplasm; typically cytolytic

    • Fecal-oral transmission is common; usually does not cause diarrhea

  • Epidemiology

    • Asymptomatic shedding and outbreaks occur in school/daycare settings, possibly linked to sewage contamination

  • Genera include:

    • Enterovirus

    • Types: Poliovirus, Coxsackievirus A and B, Echovirus

    • Rhinovirus: Same morphology, different biochemistry

Pathogenesis of Enterovirus

  • Infection Process:

    • Viral replication occurs in oropharynx and intestine, leading to:

    • Primary viremia in bloodstream

    • Subsequent replication in lymphoid tissues

    • Secondary viremia

    • Target tissues include:

    • Rhinovirus, Echo, Coxsackie, Polio

    • Manifestations vary based on target tissue (e.g., skin, liver, brain)

    • Virus shed in feces; may lead to diverse clinical diseases including herpangina, meningitis, myocarditis, and paralysis.

Poliovirus

  • Characteristics

    • Humans are the only natural hosts; last case of wild-type polio in the US was in 1979

  • Vaccination History

    • First vaccine introduced in 1955; vaccine-associated cases can occur

    • Two types: Inactivated (formalin-killed) and oral (live)

  • Global Efforts

    • WHO's goal: eradicate polio worldwide, but cases persist in developing countries

  • Pathogenesis

    • Virus infects cells of Peyer's patches in the intestine and motor neurons; lifelong immunity results

Primary Pathogenesis Hypothesis

A. Virus ingestion leads to primary infection if ingested amount is sufficient.
B. Variable amounts of virus may enter bloodstream.
C. During the infection:

  • Virus passes through stomach to intestine, replicating rapidly in lymph nodules.
    D. Secondary infections can occur in extraneural tissues via bloodstream.
    E. The virus then reaches the CNS via neural pathways, causing various paralysis outcomes.
    F. Virus is excreted in feces, potentially spreading the infection.

Clinical Outcomes of Polio

  • Asymptomatic: Most infections are without symptoms.

  • Aseptic Meningitis: Affects 1-8% of cases, typically resolves within a week.

    • Symptoms: Fever, signs of meningeal irritation.

  • Paralytic Polio: Affects 0.1-2% of infections.

    • Features biphasic progression and can lead to:

      • Muscle pain

      • Asymmetrical flaccid paralysis

      • Possible outcomes range from paralysis of a limb to quadriplegia

      • Bulbar paralysis: affects cranial nerves, causing dysphagia and dyspnea.

Cytopathology of Poliovirus

  • Stages in Destruction of Motor Neurons

    • Diffuse chromatolysis observed in affected neurons

    • Polymorphonuclear cells penetrate necrotic neurons leading to neuron death

    • Clinically, residual paralysis may lead to severe deformities over time.

Diagnosis and Prevention of Poliovirus

  • Diagnostic Samples: Throat secretions, feces, CSF.

  • RT-PCR: Used for diagnosis, no drug therapy available.

  • Vaccines: OPV (oral polio vaccine) and IPV (inactivated polio vaccine) recommended in the US for immunocompromised.

Coxsackieviruses

General Characteristics

  • Nonenveloped, ss(+) RNA viruses, primarily replicate in the respiratory tract and distal bowel.

  • Asymptomatic infections possible.

Clinical Diseases Associated with Coxsackievirus A

  • Hand-foot-and-mouth disease: Vesicular lesions, mild fever, resolving in a few days. Common in children.

  • Herpangina: Symptoms include fever, sore throat, and vesicular ulcerated lesions; commonly seen in summer.

Clinical Diseases Associated with Coxsackievirus B

  • Pleurodynia (Bornholm disease): Severe chest pain due to viral infection of myofibers.

  • Myocardial infections leading to myocarditis; these can result in heart failure.

Aseptic Meningitis

  • Symptoms: Fever, headache, photophobia, and nuchal rigidity.

  • CSF findings: Elevated lymphocytes, normal glucose levels, increased protein level.

Diagnosis of Coxsackievirus Infections

  • Samples collected: Stool or rectal swabs, possibly CSF.

  • Detection methods include RT-PCR and viral culture (CPE in 2-6 days). Supportive treatment provided.

Rhinoviruses

  • Small, nonenveloped, ss(+) RNA viruses, specific growth at 33°C (optimum temperature).

  • Peak incidence in summer and fall; spread primarily through respiratory secretions. The main cause of common colds and URTIs.

Coronaviruses

  • Enveloped, positive (+) RNA viruses displaying club-shaped glycoproteins.

  • Replication mechanism includes generating individual mRNAs for viral protein formation.

Pathogenesis and Clinical Presentation of Alpha Coronaviruses

  • Primarily infect epithelial cells, localized infections of the upper respiratory tract seen.

  • Common in infants and children, presenting similar cold symptoms to rhinoviruses.

Pathogenesis and Clinical Presentation of Beta Coronaviruses (SARS, MERS, SAR-CoV-2)

  • Potential recombination in animals leading to more pathogenic species.

  • Intermediary hosts (civet cats for SARS) noted in zoonotic transmissions.

  • Differences in receptor binding domains for Spike proteins affect infection and pathogenicity across species.

Severe Acute Respiratory Syndrome (SARS)

  • A novel coronavirus initially infecting humans from animal sources.

  • Symptoms may include fever, myalgias, chills, dry cough indicative of lower respiratory tract involvement.

  • ICU admission required in 20-30% of cases with a notable mortality rate of 10%. Incubation period ranges from 2-10 days.

SARS Clinical Manifestations

  • Includes signs confirmations through radiographic examinations indicating lung involvement (like bilateral consolidation).

COVID-19 Pathogenesis

  • SARS-CoV-2 adaptations facilitate entry into human cells via ACE2 receptors, with Spike protein showing efficient binding mechanisms.

  • Post-infection dynamics leading to RNA translation and viral assembly emphasized.

Diagnosis and Treatment of Coronaviruses

  • Diagnostic tools include rapid antigen tests and RT-PCR assays.

  • Treatments involve antiviral medications like nirmatrelvir/ritonavir (Paxlovid) plus supportive care.

  • Vaccines, predominantly mRNA-based, and a recombinant protein vaccine available targeting the spike protein.

Flaviviruses

  • Enveloped, positive-sense ssRNA family that includes significant pathogens like:

    • St. Louis Encephalitis (SLE)

    • West Nile Virus (WNV)

    • Japanese Encephalitis (JE)

    • Yellow Fever

    • Dengue

Transmission and Pathogenesis of Flaviviruses

  • Mainly transmitted by mosquitoes such as Culex species with birds as reservoir hosts.

  • Clinical consequences can include neurological complications such as encephalitis.

Togaviruses

  • Enveloped, positive-sense ssRNA viruses, including Alphaviruses.

  • Significant types associated with encephalitic disease include Eastern, Western, and Venezuelan Equine Encephalitis.

  • Rubella assigned to Matonaviruses can cause serious congenital complications if maternal infection occurs early in pregnancy.

Influenza Virus

  • Orthomyxoviridae Family: Includes Influenza A, B, C.

  • Characteristics include spherical structure, nuclear replication (cap snatching) with a segmented (-) ssRNA genome.

  • Key proteins: Hemagglutinin (HA) and Neuraminidase (NA) are essential for viral entry and exit from host cells.

Influenza Virus Replication and Clinical Features

  • Mechanisms of virus binding to host receptors through HA causing fusion and following uncoating events that lead to transcription and replication within the cell.

  • Agonizing annual epidemics due to antigenic drift and shift observed, leading to potential pandemics associated with reassortment through mixed infections.

Clinical Manifestations and Diagnosis

  • Symptoms include acute onset with systemic manifestations like fever and myalgia. Diagnosis typically through serological assays, viral culture, or RT-PCR.

  • Treatment options include antiviral therapy targeting the neuraminidase protein and the uncoating mechanism, distinguishing between A and B strains.

Paramyxoviruses

  • Characteristics of this family include (-) ssRNA genome with associated proteins involved in viral attachment and fusion.

  • Major pathogens: Measles, Mumps, Respiratory Syncytial Virus.

Measles Virus Pathogenesis

  • Primary replication occurs in the respiratory tract; symptoms manifest through viremia leading to characteristic rash prompted by immune response.

  • Koplik spots serve as an early diagnostic indicator preceding the rash.

Clinical Outcomes of Measles

  • Phases include incubation, prodromal symptoms (high fever, cough), and exanthematous stage.

Diagnosis and Management

  • Clinical presentation is critical, requiring confirmation through serological testing and monitoring for complications.

Mumps Virus

  • Enveloped (-) ssRNA virus with transmission through close person-to-person contact.

  • Symptoms consist of nonspecific illness evolving towards parotitis and various complications.

Rabies Virus Overview

  • Negative-sense ssRNA virus characterized structurally by a unique shape and specific glycoprotein for receptor interactions.

Pathogenesis of Rabies

  • Infection initiated through bites or tissue transplants; the variable incubation time leads to extensive viral movement and replication in nervous tissues.

  • Manifestations include a prodrome followed by neurologic involvement with potential respiratory failure leading to mortality.

Diagnosis and Treatment of Rabies

  • Diagnostic evidence relies on exposure history, lab confirmation through various biologic samples, and treatment post-exposure regimens crucial for preventing clinical disease progression.