Principles of Medical Virology¶
Chapter 195 | Part 5: Infectious Diseases
KEY CLINICAL POINTS¶
- Viruses are obligate intracellular parasites requiring host cells for replication, with genomes of RNA or DNA and protein coats.
- Classification of viruses is based on genome type, capsid symmetry, envelope presence, and replication strategies (e.g., positive-strand RNA, negative-strand RNA, DNA viruses).
- Viral replication involves binding, entry, uncoating, transcription, translation, assembly, and release, with mechanisms varying by viral family.
- Detection methods include electron microscopy, PCR, and serologic assays, while treatment depends on viral type (e.g., azithromycin for Chlamydia pneumoniae).
- Host immune responses (innate and adaptive) play critical roles in controlling viral infections, with antiviral mechanisms including IFN production and T-cell-mediated clearance.
1. DEFINITION & OVERVIEW¶
Viruses are obligate intracellular parasites that must enter host cells to replicate. They consist of nucleic acid (DNA/RNA) enclosed in a protein coat (capsid), with some having lipid envelopes. Viruses hijack host cellular machinery for replication, leading to cytopathic effects (CPE) and potential cell death. They are classified into families based on genome type, structure, and replication mechanisms.
Table 195-1 Major Families of Human Pathogenic Viruses¶
| FAMILY | REPRESENTATIVE VIRUSES | TYPE OF RNA/DNA | LIPID ENVELOPE |
|---|---|---|---|
| Picornaviridae | Coxsackievirus, Echovirus, Poliovirus, Rhinovirus, Hepatitis A virus | (+) RNA | No |
| Caliciviridae | Norovirus | (+) RNA | No |
| Hepeviridae | Hepatitis E virus | (+) RNA | No |
| Togaviridae | Eastern equine encephalitis virus, Western equine encephalitis virus | (+) RNA | Yes |
| Flaviviridae | Yellow fever virus, Dengue virus, West Nile virus, Zika virus | (+) RNA | Yes |
| Coronaviridae | SARS-CoV-1, SARS-Co, Middle East respiratory syndrome virus | (+) RNA | Yes |
| Rhabdoviridae | Rabies virus | (–) RNA | Yes |
| Filoviridae | Marburg virus, Ebola virus | (–) RNA | Yes |
| FAMILY | REPRESENTATIVE VIRUSES | TYPE OF RNA/DNA | LIPID ENVELOPE |
|---|---|---|---|
| Pneumoviridae | Respiratory syncytial virus | (–) RNA | Yes |
| Paramyxoviridae | Parainfluenza virus, Mumps virus, Measles virus | (–) RNA | Yes |
| Orthomyxoviridae | Influenza A, B, and C viruses | (–) RNA, 8 segments | Yes |
| Peribunyaviridae | California encephalitis virus | (–) RNA, 3 segments | Yes |
| Hantaviridae | Hantavirus | (–) RNA, 3 segments | Yes |
| Nairoviridae | Crimean–Congo hemorrhagic fever virus | (–) RNA, 3 segments | Yes |
| Arenaviridae | Lymphocytic choriomeningitis virus, Lassa fever virus | (–) RNA, 2 segments | Yes |
| Retroviridae | Human T lymphotropic virus 1 and 2, Human immunodeficiency virus 1 and 2 | (+) RNA, 2 identical segments | Yes |
| Hepadnaviridae | Hepatitis B virus | dsDNA with ss portions | Yes |
| Parvoviridae | Parvovirus B19 | ssDNA | No |
| Papillomaviridae | Human papillomaviruses | dsDNA | No |
| Polyomaviridae | JC virus, BK virus, Merkel cell polyoma virus | dsDNA | No |
| Adenoviridae | Human adenoviruses | dsDNA | No |
| Orthoherpesviridae | Herpes simplex virus 1 and 2, Varicella-zoster virus, Epstein-Barr virus, Cytomegalovirus | dsDNA | Yes |
| Poxviridae | Variola (smallpox) virus | dsDNA | Yes |
1.1 Viral Structure¶
Viruses have three main components: nucleic acid (genome), capsid (protein coat), and sometimes an envelope. Capsids are formed from repeating protein subunits (capsomers) and exhibit icosahedral, helical, or complex symmetry. Enveloped viruses (e.g., influenza) have lipid membranes derived from host cells, while nonenveloped viruses (e.g., poliovirus) rely on protein shells for protection.
1.2 Classification¶
Viruses are classified into families based on genome type (DNA/RNA), strandedness (single/double), capsid symmetry, and replication strategies. Major families include Picornaviridae (e.g., poliovirus), Orthomyxoviridae (e.g., influenza), and Herpesviridae (e.g., HSV).
2. ETIOLOGY & PATHOPHYSIOLOGY¶
Viruses replicate by hijacking host cellular machinery. Positive-strand RNA viruses (e.g., picornaviruses) are translated directly into polyproteins, while negative-strand RNA viruses (e.g., influenza) require viral RNA-dependent RNA polymerase to transcribe mRNA. DNA viruses (e.g., herpesviruses) replicate in the nucleus, and retroviruses (e.g., HIV) reverse transcribe RNA into DNA and integrate into host chromosomes. Viral replication strategies vary by genome type and structure.
2.1 Viral Replication Strategies¶
Positive-strand RNA viruses (e.g., picornaviruses) are translated directly into polyproteins, which are cleaved into structural and nonstructural proteins. Negative-strand RNA viruses (e.g., influenza) require viral RNA-dependent RNA polymerase to transcribe mRNA. DNA viruses (e.g., herpesviruses) replicate in the nucleus, while retroviruses (e.g., HIV) reverse transcribe RNA into DNA and integrate into host chromosomes.
2.2 Host Cell Effects¶
Viruses inhibit host cell processes (e.g., transcription, protein synthesis) to optimize replication. This can lead to cell injury, apoptosis, or necrosis. Some viruses (e.g., papillomaviruses) induce cell proliferation to support viral DNA replication.
3. INVESTIGATIONS & DIAGNOSIS¶
Viral infections are diagnosed using molecular methods (PCR), serologic assays (ELISA), and electron microscopy. Viral load quantification is achieved via RT-PCR, plaque assays, or endpoint dilution assays. Detection of viral antigens or nucleic acids in clinical specimens (e.g., blood, CSF, stool) is critical for diagnosis.
3.1 Diagnostic Techniques¶
PCR amplifies viral nucleic acids for detection, while EM visualizes virions. Serologic assays (e.g., ELISA) detect antibodies against viral antigens. Viral load is quantified using RT-PCR or plaque assays.
3.2 Viral Load Measurement¶
Viral load is measured in PFUs/mL using plaque assays or RT-PCR. For example, HSV-1 DNA can be quantified in CSF for encephalitis, and HIV load is measured in serum using automated instruments.
4. MANAGEMENT & TREATMENT¶
Treatment depends on the viral type. Chlamydia pneumoniae infections are treated with azithromycin, doxycycline, or fluoroquinolones. Antiviral drugs target specific replication steps (e.g., reverse transcriptase inhibitors for HIV). Supportive care and immune modulation are critical for managing severe infections.
4.1 Antimicrobial Therapy¶
C. pneumoniae is treated with azithromycin (500 mg once, then 250 mg days 2–5), doxycycline (100 mg twice daily), or fluoroquinolones (e.g., levofloxacin 750 mg daily). Beta-lactams and trimethoprim/sulfamethoxazole are ineffective.
4.2 Antiviral Agents¶
Antivirals target specific steps in viral replication (e.g., nucleoside analogs for HIV, neuraminidase inhibitors for influenza). Treatment duration varies by virus and clinical context.
5. PROGNOSIS & COMPLICATIONS¶
Prognosis depends on viral type, host immune status, and treatment efficacy. Persistent infections (e.g., hepatitis B, HSV) can lead to chronic disease or latency. Long-term effects (e.g., post-viral syndromes) may occur after acute infections, such as long COVID or post-polio syndrome.
5.1 Chronic Infections¶
Viruses like hepatitis B or HIV can establish chronic infections, leading to progressive organ damage. Latent infections (e.g., HSV in neurons) may reactivate under immunosuppressive conditions.
5.2 Post-Infection Syndromes¶
Persistent viral replication or immune dysregulation can cause long-term symptoms (e.g., long COVID, post-dengue fatigue). These syndromes highlight the need for further research into viral pathogenesis.
6. SPECIAL CONSIDERATIONS¶
Transmission routes vary by virus (e.g., respiratory, fecal-oral, vector-borne). Zoonotic transmission (e.g., SARS-CoV-1/2 from bats to humans) is a critical factor in emerging viral diseases. Immune status and host factors (e.g., pregnancy, immunosuppression) influence disease severity and outcomes.
6.1 Transmission Routes¶
Viruses spread via respiratory droplets (e.g., influenza), fecal-oral (e.g., norovirus), vector-borne (e.g., dengue), or direct contact (e.g., HSV). Zoonotic transmission (e.g., SARS-CoV-2 from bats) is a key mechanism for emerging pathogens.
6.2 Host Factors¶
Immune status, age, and comorbidities (e.g., diabetes, HIV) influence viral pathogenesis. For example, immunosuppressed patients are at higher risk for severe HSV or CMV infections.