Poxviridae - DNA Viruses - Medical Microbiology

DNA VIRUSES CLASSIFICATION OF VIRUSES? Criteria????????????? 1. Host types 2. Disease syndrome 3. Viral structure & symmetry 4. Nucleic acid types (Genome) 5. mRNA production mechanism 6. Modern taxonomy (Phylogenetic) CLASSIFICATION BY NUCLEIC ACID & HOST TYPE...

DNA VIRUSES CLASSIFICATION OF VIRUSES? Criteria????????????? 1. Host types 2. Disease syndrome 3. Viral structure & symmetry 4. Nucleic acid types (Genome) 5. mRNA production mechanism 6. Modern taxonomy (Phylogenetic) CLASSIFICATION BY NUCLEIC ACID & HOST TYPES BALTIMORE CLASSIFICATION OF VIRUSES Classification based on 1. the Nucleic Acid types 2. m-RNA production mechanism Classification into six groups/families BALTIMORE’S 6-GROUPS OF VIRUSES 1. ds-DNA viruses 2. ss-DNA viruses 3. ds- RNA viruses 4. ss-RNA viruses with positive strands(+ve polarity) 5. ss-RNA viruses with negative strands(-ve polarity) 6. ss-RNA viruses associated with the enzyme reverse transcriptase.  MEDICAL IMPORTANT DOUBLE STRANDED DNA VIRUSES 1. Poxviridae DNA viruses can be classified as: 2. Herpesviridae A.Enveloped viruses 3. Hepadnaviridae B.Non-enveloped viruses 4. Adenoviridae 5. Papovaviridae POXVIRIDAE  THE POXVIRIDAE Consist of many significant viruses Some cause human infection Others naturally infect animals Incidental human infections (Zoonosis) common with animal strains Many members shares antigenic determinant allowing cross protection against another Animal poxvirus are sometimes used in human vaccine  UNIQUE PROPERTIES OF POXVIRUSES Largest virus (300nm) Almost visible under compound light microscope Enveloped (But resistant to inactivation) dsDNA genome 130-375 kb Bricked shape Has dumbbell core ( Contains Nucleic Acid) Possess Lateral bodies (Unknown function) UNIQUE PROPERTIES OF POXVIRUSES Produce more than 100 polypeptide Replicates in the cytoplasm Highly species-specific Under exploration for gene therapy CLASSIFICATION OF POXVIRIDAE  REPLICATION Viral Replication is divisible into those controlled by: Early (Pre-replicative) gene products Late (Post-replicative) gene products The replication starts with Attachment & Penetration This is subsequent to viral & host cell Membrane fusion Naked DNA is not infectious  REPLICATION Viral core dissociates to release Viral DNA Viral enzymes Core enzymes (including DNA-dependent RNA polymerase play key roles in viral replication  REPLICATION Virally-encoded RNA polymerase ( prepackaged) synthesizes the Early mRNA From the Early mRNA is formed the Early Proteins: DNA polymerase Thymidine kinase Recombinase This gives room to uncoating, DNA replication and synthesis of Late mRNA Initial uncoating is due to cellular enzymes but full uncoating is by viral enzymes  REPLICATION Late mRNA leads to late proteins (Structural proteins) synthesis Virus Maturation follows assembly with synthesis & incorporation of Viral membranes Some of the mature virus exits by budding (exocytosis) but most is by cytolysis 80-90% are released by cell rupture  TRANSMISSION There are some peculiarities in the mode of transmission Small pox virus transmission is respiratory Other poxviruses are largely transmitted by contact Zoonotic transmission is common Nosocomial transmission?  PATHOGENESIS Poxvirus replication occur locally in the infected cells after acquisition This manifest as dermal hyperplasia & leukocytes infiltration And then, primary viraemia follows Dissemination is especially to lymph nodes via: Lymphatics and Cell (macrophages) mediated spread  PATHOGENESIS Virus multiplies further in seeded lymph nodes This leads to: Secondary viraemia Another dermal inoculation Characteristic Skin eruption (Pocks)  EPIDEMIOLOGY Small pox & molluscum contagiosum are strictly human viruses Natural host for other poxviruses are vertebrate other than man Zoonosis occurs by: accidental inoculation occupational hazard  POXVIRUSES PATHOGENIC FOR MAN Virus Primary Disease Host Molluscum Humans Multiple & long lasting Skin nodules contagiosum Milkers nodes Cattle Skin lesion similar to cowpox virus Monkeypox virus Squirrels? Resembles human smallpox Smallpox virus Humans Generalized infection with pustular rash Vaccinia virus No Rare complication of vaccination generalized  CLINICAL MANIFESTATION Poxviruses produces characteristic skin rashes Most poxvirus typically have a primary lesion Generalized lesion develops in human monkeypox & molluscum Cowpox & Parapox infections develop at inoculation site (hands usually) They then spread to other sites (face, genitals by scratching) Human monkeypox resembles mild smallpox  CLINICAL MANIFESTATION Parapox and molluscum are painless & cause little disturbance Human cowpox is very painful & cause fever, lymphadenopathy It often also require hospitalization especially in children Encephalitis may complicate cowpox Erythema multiforme is a complication of parapox Severe infection with generalized illness can be precipitated by: Immunocompromised state Eczema CLINICAL MANIFESTATION DIAGNOSIS o Clinical Diagnosis o Definitive diagnosis  CLINICAL DIAGNOSIS o Watch for Symptoms o Most important clinical indicator is Medical history History of contact Occupational history Exposure to wildlife Exposure to infected patients o History of rash and its evolution  DEFINITIVE DIAGNOSIS 1. Electron microscopy 4. PCR 2. ELISA – a. Antigen Detection (Antigen capture) b. Serology (Antibody capture) -ELISA is not reliable Cross reactivity with other OPV -IFA 3. Viral isolation by culture  TREATMENT o Disease is self-limiting o Treatment is largely supportive o Supportive treatment directed at SYMPTOMS o Supportive care used to prevent/ manage severe and distressful disease/ complications o Mx of comorbidity also important  PREVENTION Vaccination is the major tool Vaccinia vaccine used to eradicate smallpox (Variola disease) Same vaccine is being used in outbreak for monkeypox Nosocomial spread control is very important