RNA Viruses - Copy

Microbiology: RNA Viruses

Picornaviridae Enterovirus

  • Poliovirus Characteristics:
    • RNA virus.
    • Icosahedral nucleocapsid.
    • Non-enveloped.
    • Single-stranded positive-sense RNA (SS+).
    • Non-segmented genome.
  • Clinical Presentation:
    • Paralytic poliomyelitis.
    • Aseptic meningitis.
    • Abortive poliomyelitis (sore throat, malaise).
  • Pathobiology:
    • Transmitted via the fecal-oral route.
    • Travels to the GI tract and is stable at low gastric pH.
    • Infects the epithelium of the small intestine and oral pharynx.
    • Replicates in submucosal lymphoid tissue (Peyer’s patches, tonsils).
    • Transient viremia spreads to the CNS via viremia and/or retrograde transport in peripheral nerves (exact mechanism unknown).
    • Binds to receptors on anterior horn motor neurons and replicates.
    • Causes lysis of motor neurons innervating distal muscles (lower motor neuron disease) or proximal muscles (respiratory insufficiency and possible death).
    • Infection generates IgG and secretory IgA to protect against future infections.
  • Diagnosis:
    • In meningitis, look for increased lymphocytes, normal glucose, and normal to increased protein levels in CSF.
    • Collect throat, stool, or spinal specimens.
    • Isolate and observe the cytopathic effect (harmful effects on host cells).
    • Serology.
  • Treatment:
    • Symptomatic support.
    • Passive immunization with IgG vaccines:
      • Inactivated Polio Vaccine (Salk vaccine): killed virus.
      • Oral Polio Vaccine (Sabin vaccine): live, attenuated virus.
  • Epidemiology and Complications:
    • Polio has been eradicated in the Western Hemisphere.
    • Rare cases occur when OPV reverts to virulence.
    • Post-paralytic syndrome occurs years after initial infection, presenting as gradual muscle wasting.
  • Clinical Case:
    • A woman in India presents with fever, muscle pains, and weakness in her trunk, abdomen, and legs.
    • She reports difficulty swallowing and neck pain.
    • Physical exam reveals fasciculations and flaccid paralysis of the lower limbs and trunk, along with troubled breathing.
    • CSF analysis shows lymphocytosis, PMNs, and normal glucose and protein levels.

Coxsackieviruses A & B

  • Characteristics:
    • Picornaviridiae Enterovirus.
    • RNA virus, icosahedral nucleocapsid, non-enveloped, SS+ non-segmented.
  • Clinical Presentation:
    • Coxsackie A: herpangina, hand-foot-and-mouth disease.
    • Coxsackie B: pleurodynia, myocarditis, and pericarditis.
    • A or B: aseptic meningitis, paralysis, upper respiratory tract infection.
  • Pathobiology:
    • Typical in summer and fall.
    • Fecal-oral or aerosol transmission.
    • Travels in the GI tract (stable in low gastric pH).
    • Infects mucosal epithelial cells, replicates, and spreads, leading to viremia and cell lysis.
    • Skin and mucosal epithelium (Group A): vesicles, causing herpangina (red oropharynx vesicles and sore throat) and hand-foot-and-mouth disease.
    • Heart and pleural surfaces (Group B): pleurodynia, myocarditis, and pericarditis.
    • Meninges and anterior horn motor neurons (Group A or B): aseptic meningitis and paralysis.
  • Diagnosis:
    • Isolate the virus and serology.
  • Treatment:
    • Symptomatic treatment with anti-inflammatory agents.
    • No antivirals or vaccines available.
  • Quick Facts:
    • The most common causes of aseptic meningitis are Coxsackievirus, Echovirus, and Mumps virus.
    • Palm and Sole rash differential: Syphilis, Rocky Mountain spotted fever, and Coxsackievirus.
    • Coxsackievirus B is associated with 50% of cases of viral myocarditis.
    • ECHO viruses (Enteric Cytopathic Human Orphan): cause disease similar to coxsackievirus group.
    • Other strains of enteroviruses are the leading cause of acute hemorrhagic conjunctivitis.
  • Clinical Case:
    • A young man presents with chest pain, dyspnea, and early signs of heart failure.
    • His history shows he had an upper respiratory infection 3 weeks ago.
    • Exam reveals tachycardia.
    • ECG shows evidence of a conduction defect.
    • Echocardiogram shows cardiomegaly with contractile dysfunction.
    • Diagnosis made via serology, patient most likely will recover completely.

Hepatitis A Virus

  • Characteristics:
    • Picornaviridae Enterovirus.
    • RNA virus, icosahedral nucleocapsid, non-enveloped, SS+ non-segmented.
  • Clinical:
    • Acute Hepatitis.
  • Pathobiology:
    • Transmitted by the fecal-oral route.
    • Travels in the GI tract (stable at low gastric pH).
    • Infects mucosal epithelial cells and replicates, spreads (viremia), and reaches the liver by the portal circulation, infecting hepatocytes.
    • CTL response is stimulated, killing infected hepatocytes.
    • Often asymptomatic but may cause jaundice.
  • Diagnosis:
    • IgM detection in serum (IgG indicates past infections).
  • Treatment:
    • Supportive care, pooled immune globulins, and vaccine: formalin-inactivated HAV.
  • Epidemiology:
    • Epidemics among children are the most frequent cases (summer camps and schools).
    • Most adults have been asymptomatically infected, as evidenced by anti-HAV IgG.
  • Key Points:
    • HAV and HEV: oral transmission, no chronic carrier state, cirrhosis, or hepatocellular carcinoma.

Rhinovirus

  • Characteristics:
    • Picornaviridae.
    • RNA virus, icosahedral nucleocapsid, non-enveloped, SS+ non-segmented.
  • Clinical:
    • Common cold.
  • Pathobiology:
    • Only a human reservoir.
    • Spreads by contact or aerosol.
    • Binds ICAM-1 on upper respiratory tract epithelial cells and extends locally without killing cells.
    • Local inflammation causes exudate.
    • Increased ICAM-1 expression leads to further viral binding and infection.
    • Exudates may block passageways, leading to secondary bacterial sinusitis or otitis media.
    • Acquired IgA immunity to a particular serotype after infection.
  • Diagnosis:
    • Symptoms.
  • Treatment:
    • Supportive care.
    • No vaccine because there are too many viral serotypes.
  • Quick Facts:
    • 50% of colds are due to rhinovirus.
    • Rhinovirus preferentially replicates at the cooler 33 °C of the nose and upper airways.
    • The warmer 37 °C of the lungs precludes rhinovirus pneumonia.
    • Causes of the common cold: Rhinovirus, Coronavirus, Adenovirus, Influenza C virus, and Coxsackievirus.
  • Clinical Case:
    • A woman presents with a runny nose, sneezing, an irritable throat, and a slight fever.
    • She suffers similar symptoms every year, often at the same time as other members of her family.
    • Her symptoms go away in a week, except for the nasal discharge that persists for a few more days.

Caliciviridae Calicivirus

  • Norwalk Virus Characteristics:
    • RNA viruses, icosahedral nucleocapsid, non-enveloped, SS+ non-segmented.
  • Clinical Presentation:
    • Gastroenteritis.
  • Pathobiology:
    • Transmitted by contact or contaminated food and water.
    • Local infection and inflammation in the proximal small intestine lead to gastroenteritis.
  • Diagnosis:
    • Not typically done, but a stool specimen can be ordered to visualize the virus.
  • Treatment:
    • Usually not required because it is self-limited.
    • Rehydration for severe fluid loss.
  • Clinical Case:
    • Thirteen people attending an oyster dinner abruptly developed nausea and abdominal pain 2 days later.
    • Soon after the onset of pain, they begin to vomit, and some also have diarrhea.
    • Norwalk virus is a significant cause of group-related or institutional diarrhea.

Hepeviridae Hepevirus

  • Hepatitis E Virus Characteristics:
    • RNA virus, icosahedral nucleocapsid, non-enveloped, SS+ non-segmented.
  • Clinical Presentation:
    • Acute hepatitis.
  • Pathobiology:
    • Transmitted by the fecal-oral route.
    • Travels in the GI tract (stable at low gastric pH) and infects mucosal epithelial cells.
    • Replicates and spreads (viremia), reaching the liver by portal circulation and infecting hepatocytes.
    • CTL response stimulates the killing of infected hepatocytes, which may be asymptomatic but cause jaundice.
  • Diagnosis:
    • Symptoms, rule out HAV.
  • Treatment:
    • None developed.
  • Key Points:
    • HEV resembles HAV but is also associated with high mortality in pregnant women.
    • Hepatitis E may be responsible for two-thirds of epidemic “non-A, non-B” hepatitis cases in India, Russia, and other Asian countries.
  • Clinical Case:
    • A man goes to India on a hiking trip in the Himalayas.
    • Upon returning, he develops nausea, vomiting, malaise, and headache.
    • His doctor notices jaundice and hepatomegaly on physical exam, and labs detect increased AST, ALT, and direct serum bilirubin levels.
    • Immunization records show that the man had received HAV and JBV vaccines before leaving.
    • The symptoms are traced back to a shared water supply along the hiking route.

Reoviridae Rotavirus

  • Characteristics:
    • RNA virus, icosahedral nucleocapsid, non-enveloped.
    • Double-stranded (DS), segmented genome with 11 segments of dsRNA, allowing for frequent gene reassortment.
  • Clinical Presentation:
    • Gastroenteritis.
  • Pathobiology:
    • Transmitted via the fecal-oral route.
    • Infects villus cells of the proximal small intestine and replicates within the cell causing lysis.
    • Impaired absorption of carbs and other nutrients.
    • Vomiting followed by diarrhea.
  • Diagnosis:
    • Stool specimen: immunoassay for virus.
  • Treatment:
    • Rehydration and rotavirus vaccine (live oral attenuated).
  • Key Points:
    • Because rotaviruses cause no inflammation, diarrhea has no blood.
    • Infection before 6 months is uncommon due to passive IgA immunity from the mother’s colostrum.
    • By age 3, almost every individual worldwide has been infected and develops lifelong immunity.
    • REO = respiratory enteric orphan (because once not associated with any disease).
    • Reoviruses are the only RNA viruses that are double-stranded.
  • Clinical Case:
    • A mother brings her 3-year-old son to the doctor after severe bouts of vomiting and diarrhea for the past 2 days.
    • The diarrhea is watery, with no blood.
    • The doctor makes a diagnosis by an ELISA on the child’s stool and recommends rehydration.

Reoviridae Coltivirus

  • Colorado Tick Virus Characteristics:
    • RNA virus, icosahedral nucleocapsid, non-enveloped, DS segmented.
    • Genome has 10 segments of ds RNA, allowing for frequent reassortment.
  • Clinical Presentation:
    • Fever, myalgias, ocular pain, and headache.
  • Pathobiology:
    • Carried in rodents, transferred to humans via wood tick bite.
    • The virus may spread systemically (viremia).
    • The virus may infect and cause lesions in any body organ.
    • If the virus infects bone marrow cells and infected erythrocytes, leukopenia and thrombocytopenia may result.
  • Diagnosis:
    • Serology, isolation of virus from blood, and detection of viral antigens on erythrocytes.
  • Treatment:
    • None available.
  • Epidemiology:
    • Endemic to Rocky Mountains where hikers or campers are often infected following tick bites.
  • Differential Diagnosis:
    • RMSF and Tularemia.
  • Clinical Case:
    • A hiker in the Rocky Mountains complains of fever and muscle aches.
    • The symptoms have worsened since the day before, and he feels head and neck pain upon movement.
    • He affirms he was bitten several times by ticks.
    • The ranger informs the hiker that several hundred people suffer the same infection every year and instructs him to report to the base hospital and avoid aspirin or sharp bruising hits for fear of hemorrhage.

Togaviridae Alphavirus

  • Geography:
    • Eastern Equine Encephalitis (EEE) localizes to swampy areas of the U.S. eastern coast.
    • Western Equine Encephalitis (WEE) localizes to western and central U.S. and Canada.
    • Venezuelan Equine Encephalitis (VEE) localizes to Venezuela, Colombia, Central America, and Texas.
  • Characteristics:
    • RNA virus, icosahedral nucleocapsid, enveloped, SS+ non-segmented.
  • Clinical Presentation:
    • Encephalitis.
  • Pathobiology (EEE, WEE, VEE):
    • Carried in birds or horses, transferred to humans via a mosquito bite.
    • Enters circulation and infects the endothelial, reticuloendothelial, and lyses cells to produce primary viremia.
    • If the viremia persists, it infects CNS endothelial cells and neurons, resulting in hemorrhage, inflammation, and necrosis.
    • CNS symptoms include headache, meningitis, and photophobia.
    • High mortality rate (EEE > WEE > VEE).
  • Key Term:
    • ARBOVIRUS = mosquito Arthropod-borne virus:
      • Togaviridae: WEE, EEE, VEE
      • Flavivirus: West Nile virus, Yellow Fever, Dengue, St. Louis encephalitis, and Japanese encephalitis.
      • Bunyaviridae: California encephalitis, Rift Valley Fever, and Sandfly Fever.
  • Clinical Case:
    • In late July, a father brings his daughter to the ED for fever, vomiting, and strange behavior.
    • The daughter has head and neck pains and is photophobic.
    • A quick neurological exam revealed hemiparesis and some cranial nerve deficits.
    • The father affirms that they are swarmed by mosquitoes in their Florida home.
    • The doctor fears a grave diagnosis with a high mortality rate or at least a slow recovery lasting weeks.
    • The diagnosis is confirmed by the detection of the virus, PMN pleocytosis, normal glucose, and slightly increased proteins in the CSF.

Togaviridae Rubivirus

  • Characteristics:
    • Rubella virus, German Measles.
    • RNA viruses, icosahedral nucleocapsid, enveloped, SS+ non-segmented.
  • Clinical Presentation:
    • Rubella: fever followed by descending rash.
    • Congenital Rubella: congenital malformation (deafness, patent ductus arteriosus, pulmonary artery stenosis, cataracts, and microcephaly).
  • Transmission Information:
    • Droplets are relatively large particles of respiratory secretions expelled when an infected person coughs, sneezes, talks, or sings. They tend to fall to the ground or onto surfaces within a short distance (typically within 1-2 meters or 6 feet).
    • Aerosols are smaller particles that can remain suspended in the air for longer periods. They can travel further than droplets, potentially beyond the 6-foot range.
    • Airborne transmission refers to the spread of an infectious agent through the inhalation of infectious aerosols.
  • Pathobiology:
    • Transmitted by aerosol.
    • The virus infects the nasopharynx and replicates in local lymph nodes.
    • Systemic spread via blood (viremia).
    • Antibody-mediated reaction leads to maculopapular rash beginning in face and spreading to the extremities.
    • The antibody complexes may result in arthritis in women.
    • If it infects a pregnant woman in the first trimester, it may cross the placenta to the fetus.
    • Infects fetal cells and promotes mitotic arrest, necrosis, or chromosomal damage.
    • Congenital defects in the brain, heart, or eyes.
    • There is lifelong immunity following infection.
  • Diagnosis:
    • Detection of anti-rubella antibodies.
      • IgM: recent infection.
      • IgG: if immune.
    • Blocks the CPE of the ECHO virus in culture.
  • Treatment:
    • Self-limiting.
    • Vaccine: live-attenuated rubella virus in measles-mumps-rubella (MMR) vaccine.
  • TORCHES Infections:
    • TORCHES are organisms that cross the placenta and allow infection to pass from the pregnant mother to the fetus: Toxoplasmosis, Rubella, Cytomegalovirus, Herpes, HIV, Syphilis.
  • Five Most Common Peds Diseases with Rash:
    • Measles (measles virus).
    • Rubella (German measles).
    • Scarlet Fever (S. pyogenes).
    • Roseola (HHV-6).
    • Erythema infectiosum (Parvovirus B19).
  • Clinical Case:
    • A woman goes to her doctor complaining of a red rash on her face.
    • She reports having a fever that resolved just before the rash appeared.
    • The rash has spread to the arms.
    • Swollen lymph nodes are felt in the cervical region and behind the ears.
    • The doctor inquires about the woman’s vaccination record and makes a diagnosis to be confirmed by serological studies.
    • The doctor also makes sure the woman is not pregnant.
    • The rash will disappear in several days, although she may experience arthritis for some time thereafter.

Flaviviridae Flavivirus

  • West Nile Virus Characteristics:
    • RNA viruses, icosahedral nucleocapsid, enveloped, SS+ non-segmented.
  • Clinical Presentation:
    • Most infections are asymptomatic.
    • West Nile Fever symptoms include fever, fatigue, headache, myalgia, anorexia, eye pain, nausea, vomiting, diarrhea, and rash.
    • West Nile Encephalitis is a neuroinvasive disease that causes encephalitis (more typical in the elderly) or meningitis (more typical in children).
    • Symptoms range from mild confusion to tremor, extrapyramidal symptoms, flaccid paralysis, or severe encephalopathy that may progress to coma or death, particularly in the elderly or immunocompromised.
  • Pathobiology:
    • The virus is maintained in a cycle between birds and mosquitoes.
    • It spreads to an incidental human host through a mosquito bite.
    • It replicates in the skin (Langerhans cells, which migrate to regional lymph nodes) and causes viremia and infection of multiple organs, including the CNS.
  • Extrapyramidal Symptoms:
    • Dystonia: Involuntary muscle contraction causing abnormal posture and movements.
    • Akathisia: a feeling of restlessness, unable to sit still.
    • Parkinsonism: Parkinson’s disease-like symptoms (slow movements, tremors, and rigidity).
    • Tardive Dyskinesia: Involuntary repetitive movements of the face and tongue.
  • Diagnosis:
    • IgM antibody in serum or CSF.
    • PCR of CSF.
  • Treatment:
    • Supportive.
  • Prevention:
    • Mosquito control.
  • Epidemiology:
    • West Nile virus is named after the West Nile province of Uganda, where it was first isolated.
    • It first appeared in North America in 1999, causing several deaths in NY.
    • Crows and other birds are the hosts for West Nile virus.
    • Rare transmission has been reported via transfused blood products, donated organs, and breast milk.
  • Clinical Case:
    • A 75-year-old man from NY is brought to the ED after reporting 1 week of fever, headache, nausea, and muscle aches.
    • On exam, he appears confused and has a coarse tremor in his hands.
    • CT and MRI are unrevealing.
    • An LP is done, and CSF analysis demonstrates elevated protein, normal glucose, and lymphocytosis.
    • His family reports that they have avoided the outdoors after several dead crows were found in the neighborhood.

Yellow Fever, Dengue Fever, St. Louis, and Japanese Encephalitis Viruses

  • Characteristics:
    • RNA, icosahedral nucleocapsid, enveloped, SS+ non-segmented; Flaviviridae, Flavivirus.
  • Clinical Presentation:
    • Yellow Fever Virus: fever, hepatitis, and jaundice.
    • Dengue Fever: “breakbone fever” (flu-like symptoms + severe joint/muscle pain).
    • Dengue Hemorrhagic Fever: (Dengue fever + hemorrhage and shock).
    • St. Louis and Japanese Encephalitis: encephalitis.
  • Pathobiology:
    • Normal reservoir in monkeys, birds, or humans; transmitted by a mosquito bite.
    • Enters the bloodstream with transient viremia.
    • Infects:
      • Hepatocytes (Yellow Fever): necrosis, hepatitis, and jaundice.
      • Macrophages (Dengue Fever): acute inflammation, pyrogens, and pain mediators released “breakbone fever”.
      • If a second infection by a different serotype occurs, antibodies against the first serotype increase, cross-react to form immune complexes (type III hypersensitivity reaction, hemorrhage shock (Dengue Hemorrhagic Fever).
      • CNS (ST. Louis or Japanese Encephalitis): directly damages neurons, causes inflammation, and neurological abnormalities.
  • Diagnosis:
    • Isolate virus from infected tissue (from CSF in encephalitis), serology.
  • Treatment:
    • Prevention: monitor mosquito count in an area.
    • Vaccine: Yellow Fever live–attenuated vaccine and Japanese Encephalitis formalin-killed vaccine.
  • Epidemiology:
    • Epidemics have geographic specificity:
      • Yellow Fever: tropical South America and Africa.
      • Dengue: tropics worldwide. Dengue Hemorrhagic Fever: southern Asia.
      • St. Louis encephalitis: southeaster U.S.
      • Japanese encephalitis: Japan.
  • Key Points:
    • Most common human disease caused by an arbovirus is Dengue fever.
    • The most common cause of epidemic encephalitis is Japanese encephalitis.
  • Clinical Cases:
    • Case 1: A diplomat planning to travel to Central America is immunized against a possible infection that causes jaundice, hemorrhage, and liver dysfunction.
    • Case 2: A woman visits the tropics and experiences fever, headache, pain behind the eyes, in the back, and in the joints, along with a generalized rash.

Flaviviridae Hepatitis C Virus

  • Characteristics:
    • RNA viruses, icosahedral nucleocapsid, enveloped, SS+ non-segmented.
  • Clinical Presentation:
    • Acute hepatitis: jaundice, and fever
    • Chronic hepatitis: carrier state (asymptomatic), cirrhosis, predisposes to hepatocellular carcinoma.
  • Pathobiology:
    • Human reservoir, transmission by blood (especially transfusion and IV drug use), semen, and in utero.
    • The virus infects hepatocytes, and the immune response by CTLs kills infected hepatocytes, resulting in acute hepatitis in 50-70% of cases.
    • If the virus is not eliminated; the patient may develop chronic hepatitis. Usually, this patient is an asymptomatic carrier state or may develop chronic active hepatitis, cirrhosis, or predisposition to hepatocellular carcinoma.
  • Diagnosis:
    • Serology for anti-HCV antibody.
  • Treatment:
    • Pegylated alpha interferon, ribavirin, no vaccine available.
  • Key Points (HBV, HCV, HDV):
    • Blood transmission.
    • Chronic carrier state.
    • Cirrhosis.
    • Hepatocellular carcinoma.
  • Clinical Case:
    • A man presents with fatigue and reduced liver size.
    • History reveals jaundice 5 years ago following a car accident for which he received a blood transfusion.
    • Elevated serum level of ALT is noted, and an ELISA is ordered to differentiate the causes of the illness.

Retroviridae Lentivirus HIV-1, HIV-2

  • Characteristics:
    • RNA viruses, icosahedral nucleocapsid, enveloped, SS+ diploid.
  • Clinical Presentation:
    • AIDS and opportunistic infections.
  • Diagnosis:
    • Virus detection by ELISA, Western blot, PCR, HIV 1, HIV 2 antibody testing.
  • Treatment:
    • NRTI (nucleoside reverse transcriptase inhibitors): AZT, DDI, Lamivudine, Abacavir, Tenofovir, Emtricitabine.
    • NNRTI (non-nucleoside reverse transcriptase inhibitors): Efavirenz, nevirapine, delavirdine.
    • PI (protein inhibitors): indinavir, nelfinavir.
    • FI (fusion inhibitors): enfuvirtide.
    • HAART (highly active antiretroviral therapy): NNRTI + 2 NRTIs. Initiated for symptomatic HIV or CD4 count.
  • Prevention:
    • Protected sex, screening blood, and AZT for infected pregnant mothers.
  • Pathobiology:
    • Primary Infection Stage (first months):
      • Transmission by bodily fluids, sexual contact, blood transfer, maternal transfer.
      • Infects CD4+ cells (T lymphocytes in blood and macrophages in epidermis).
      • Replicates in the spleen and lymphoid organs, leading to viremia.
      • Host immune response, mononucleosis-like symptoms.
    • Clinical Latency Stage (7-10 years):
      • Mutations in antigens help the virus evade host response.
      • Virus replicates in lymphoid organs.
      • Increased T cell production, viral evasion through mutations, increased viral load, and decreased CD4+ count.
      • CD4+ cells depleted by various mechanisms.
    • Advanced Disease/ (AIDS):
      • CD4+ T-cell count <200 cells/µL.
      • Opportunistic infections/neoplasms.
      • Examples: Pneumocystis jirovecii pneumonia, Candida albicans thrush, Disseminated HSV, CMV, histoplasmosis, toxoplasmosis, cryptococcal meningitis. Mycobacterium TB, Mycobacterium avium-intracellulare, Kaposi’s sarcoma (HHV-8).
      • Infection of brain microglia, oligodendrocytes, and astrocytes leads to neuropathy, encephalopathy, and dementia.
    • HIV-1 and HIV-2 have similar clinical presentations and share common antigens; HIV-1 is found throughout the world, whereas HIV-2 is found mainly in West Africa.
  • Clinical Case:
    • A 45-year-old homeless man complains of fever, cough, and chest pain.
    • Symptoms have lingered for several weeks, and weight loss is noted.
    • Chest X-ray reveals a faint interstitial infiltrate.
      • Lab results reveal the presence of Pneumocystis jirovecii confirmed by PCR.
      • WBC 2,000 cells/µL and CD4+ T-cell count of 500 cells/µL.

Human T-cell Lymphotropic Virus

  • HTLV -1 and HTLV-2 Characteristics:
    • RNA viruses, icosahedral nucleocapsid, enveloped, SS+ diploid.
  • Clinical Presentation:
    • T-cell leukemia, lymphoma, and tropical paraparesis.
  • Pathobiology:
    • Transmission by sexual contact or blood transfer.
    • Infection of CD4+ T-cells, proviral DNA integrates into the genome.
    • Increase production of cytokines and cytokine receptors leads to IL-2, promotes hyperproliferation of infected cells, rapidly dividing cells accumulate mutations, transformation, T-cell leukemia, lymphoma.
    • If infected of CNS, antibodies produces and CTL activated, attack neural cells, weakness and stiffness in legs (tropic spastic paraparesis).
  • Diagnosis:
    • Antibody titers in serum, CSF.
  • Treatment:
    • Supportive.

Deltavirus Hepatitis D virus

  • Characteristics:

    • RNA viruses, icosahedral nucleoside, enveloped, SS negative circular.

  • Clinical Presentation:

    • Hepatitis D.

  • Pathobiology:

    • Transmitted through blood, sexual contact, or transplacentally, travels in blood to hepatocytes, infect cells, replicates and released only form those cells also infected with HBV, because it requires hepatitis B surface antigen to form infectious particle (HDV is defective and cannot replicate alone).
    • Viral antigens on infected hepatocytes recognized by host immune response leads to CTL activated resulting in inflammation, hepatocyte necrosis. Hepatitis more severe than hepatitis B alone.

  • Diagnosis:

    • Delta antigen detection, anti-delta antigen IgM antibodies.

  • Treatment:

    • Alpha IFN controls HBF infection, which limits HDV infection vaccine; recombinant Hepatitis B Surface Antigen to prevent HBV infection.

  • Key Points:

    • The HDV genome is a ribozyme, which is an RNA particle able to cleave and ligate itself. No other human viruses behave this way, but many plant viruses in the viroid group do.

Coronaviridae Coronavirus

  • Characteristics:
    • RNA virus, helical nucleoside, enveloped, SS+ non-segemented.
  • Clinical Presentation:
    • Common cold.
  • Pathobiology:
    • Transmission by respiratory secretions, virus infects upper respiratory tract cells, 3-day incubation, 6-7 days common cold.
  • Diagnosis:
    • Serology.
  • Treatment:
    • No treatment, vaccine developed not FDA approved.
  • Quick Facts:
    • Coronavirus infections account for 10-20% of common colds, second only to Rhinovirus infections. These infections are clinically indistinguishable.
    • The SARS coronavirus (SARS-CoV) is responsible for Severe Acute Respiratory Syndrome. The virus caused a deadly outbreak of viral pneumonia from 2002 to 2003, spreading from China to over 35 countries in a few weeks.
    • SARS is a rapidly progressive respiratory illness caused by coronavirus. First detected in 2002 in China. SARS commonly presents with fever, dyspnea, and cough that can progress to respiratory failure and death.
    • MERS-CoV( Middle East Respiratory Syndrome Coronavirus) human infection was first reported in 2012 in the Arabian Peninsula. Affected individuals exhibit fever, cough, and SOB, and severe complications include pneumonia and kidney failure. Diagnosis is by RT-PCR or serology. Treatment is by supportive care.

Orthomyxoviridae Influenza Virus “The Flu”

  • Characteristics:
    • RNA viruses, helical nucleocapsid, enveloped, SS negative segmented.
  • Clinical Presentation:
    • Flu and croup in children, secondary bacterial pneumonia.
  • Pathobiology:
    • Inhaled through aerosols, infects upper and lower respiratory tract ciliated epithelium via two surface proteins.
      • Hemagglutinin (HA) envelope protein binds sialic acid on cells leads to virus endocytosed.
      • Neuroaminidase (NA) envelope protein cleaves HA- sialic acid interaction to permit viral spread.
    • Replicates in and lyses cells, necrosis of epithelium, epithelial intracellular contents exposed and stimulate inflammation, macrophages produce fever via IL-1, lymphocytes produce myalgia via IFN- gamma= vasodilation and edema.
  • Symptoms:
    • Nose rhinorrhea
    • Pharynx, larynx swelling obstructs flow through sinuses and eustachian tubes croup in children with secondary sinusitis and otitis.
    • Trachea/bronchi inflammatory mucus cleared by ciliated cells lead to cough.
  • Immunity:
    • Viral shedding resolves after 2-5 days, IgA secretory immunity against viral HA and NA.
    • If infection persists, ciliary columnar epithelial cells damaged, cannot perform normal task of clearing bacteria, secondary bacterial pneumonia.
  • Diagnosis:
    • Symptoms, rapid antigen test on nasopharyngeal swab, can culture nasopharyngeal sample and detect HA via RBC agglutination test.
  • Treatment:
    • Acetaminophen, hydration, and rest.
    • Amantadine or rimantadine for influenza A and zanamivir and oseltamivir for influenza A and B.
    • Vaccine available.

Paramyxoviridae Paramyxovirus

  • Parainfluenza Viruses Characteristics:
    • RNA viruses, helical nucleocapsid, enveloped, SS negative non-segmented.
  • Clinical Presentation:
    • Children: Croup, laryngotracheobronchitis, pneumonia.
    • Adults: common cold.
  • Pathobiology:
    • Inhaled through aerosols, infects larynx mucosa via two surface antigens.
      • Hemagglutinin (HA) envelope protein binds sialic acid on cells, virus endocytosed.
      • Neuroaminidase (NA) envelope protein cleaves HA-sialic acid interaction to permit viral spread.
    • Infection progresses downward to tracheal and bronchial epithelium, inflammation and swelling of mucous membranes, narrowing of lumen obstruction of inspiration (inspiratory stridor) and expiration (barking cough) leads to croup may invade lower respiratory tract results in pneumonia.
  • Diagnosis:
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