Notes on Rhabdoviruses and Rabies Virus

Rhabdoviruses

Learning Objectives

After reading and studying this chapter, you should be able to:

  • Describe the morphology of the rabies virus.

  • Differentiate between street virus and fixed virus.

  • Understand the pathogenesis and clinical features of rabies, including Negri bodies.

  • Discuss laboratory diagnosis of rabies.

  • Explain prophylaxis against rabies.

  • Describe neural and nonneural vaccines against rabies.

Introduction

Rhabdoviruses are bullet-shaped, enveloped viruses with a single-stranded RNA genome. The term "rhabdo" derives from the Greek word for rod. The family Rhabdoviridae includes viruses that infect a wide range of hosts, including mammals, reptiles, birds, fish, insects, and plants.

Classification

Mammalian-infecting rhabdoviruses are divided into two genera:

  1. Lyssavirus: Includes the rabies virus and related viruses (e.g., Lagos bat virus).

  2. Vesiculovirus: Includes the vesicular stomatitis virus affecting livestock.

Rabies Virus

Morphology

  1. Virion Structure: The rabies virion has a helical nucleocapsid inside a bullet-shaped lipoprotein envelope, measuring 180 x 75 nm.

  2. Proteins:

    • The envelope features ~200 glycoprotein (G) spikes crucial for attachment to host cell receptors, initiating fusion and viral entry.

    • These spikes have hemagglutinin activity and contain essential antigenic sites.

  3. Matrix (M) Protein: This layer forms a core beneath the envelope, acting as the virus's major structural protein.

  4. Genome: Composed of linear, nonsegmented, negative-sense single-stranded RNA, along with an associated RNA-dependent RNA polymerase.

Resistance

Rabies virus is sensitive to ethanol, iodine solutions, and various detergents but remains stable for years if stored properly. It is sensitive to conditions like heat, sunlight, and certain chemicals.

Antigenic Properties

Rabies virus has a single serotype but exhibits strain differences based on the host species. Strains can be distinguished by monoclonal antibodies and nucleotide sequences.

  • Glycoprotein G: Important for virulence, binds neurons, and induces neutralizing antibodies.

  • Nucleoprotein: Can induce complement-fixing antibodies but isn't protective.

  • Other identified antigens include membrane proteins and RNA polymerase.

Host Range and Growth Characteristics

  • Rabies can infect all warm-blooded animals, with varying susceptibility among species.

  • Dogs are the primary reservoir for human rabies in developing areas.

Street Virus vs. Fixed Virus

  • Street Virus: The naturally occurring form that leads to rabies in humans/animals, associated with extensive neurological symptoms.

  • Fixed Virus: Produced after serial passages in lab animals, this variant is used for vaccine preparation.

Pathogenesis

  • Transmission occurs primarily through bites or scratches from rabid animals. Incubation lasts 1-12 weeks, depending on viral load, wound location, and host factors.

  • The virus multiplies at the inoculation site, eventually traveling to the CNS via retrograde axoplasmic transport.

  • CNS invasion leads to encephalitis, characterized by localized neuron degeneration and Negri bodies' formation.

Clinical Features
Humans

  • Incubation Period: Typically 1-2 months; shorter in children and severe bites.

Clinical Spectrum

  1. Prodromal Phase (2-10 days): Nonspecific symptoms like malaise, headache, nausea.

  2. Acute Neurologic Phase (2-7 days): Symptoms include hydrophobia, hallucinations, and convulsions.

  3. Coma Phase: Patients may lapse into coma, with death following due to respiratory failure.

Rabies in Dogs

  • Furious Rabies: Aggressive behavior, excessive salivation, and paralysis.

  • Dumb Rabies: Predominantly paralysis without aggression.

Laboratory Diagnosis

  • Samples from saliva, serum, and spinal fluid are analyzed for rabies antigens. Common tests include virus isolation in mice and direct immunofluorescence microscopy.

Prophylaxis

  • Post-exposure Treatment: Vaccination followed by the administration of human rabies immune globulin is crucial.

  • Pre-exposure Prophylaxis: For high-risk individuals to maintain protective antibody levels.

Vaccines

  • Neural Vaccines: Traditional but less effective; prone to vaccine failure.

  • Cell Culture Vaccines: Highly effective with fewer doses; now widely recommended.

Epidemiology

Rabies remains prevalent worldwide except for certain regions; urban rabies (from domestic animals) dominates in many areas, while sylvatic rabies (from wild animals) is also significant, especially in specific wildlife reservoirs.