Virology Lecture 3 PDF

Lecture 3 Prof. dr. Samar Solyman  RNA Viruses Picorna Viruses Toga viruses Orthomyxoviruses Rhabdo Viruses Paramyxoviruses Retroviruses  They are small RNA icosahedral naked positive sense SS RNA viruses.  They are classified into two groups: I. Enteroviruses including:...

Lecture 3 Prof. dr. Samar Solyman  RNA Viruses Picorna Viruses Toga viruses Orthomyxoviruses Rhabdo Viruses Paramyxoviruses Retroviruses  They are small RNA icosahedral naked positive sense SS RNA viruses.  They are classified into two groups: I. Enteroviruses including: - Poliovirus: 3 types  - Coxsackie A virus: 24 types  - Coxsackie B virus types 1-6 - Entero cytopathogenic human orphan virus (ECHO): 34 types  - Enteroviruses types 68-71 - Enterovirus 72 (hapatitis A virus)  They are resistant to pH 3-7, detergents, mild sewage treatment, but inactivated at 55 ˚C. II. Rhinoviruses: labile at acid pH, optimum growth temperature 33 ˚C.   a. Polioviruses ‫شلل الاطفال‬  There are three serotypes differentiated by neutralization reaction and show no cross immunity i.e. vaccination must be with the three types.  Infection is transmitted by oral-fecal means specially water and milk in children.  The incubation period is usually 10-15 days.  Clinical Forms: 1. Silent: Asymptomatic fecal carrier (the virus replicates in oropharynx and in intestine). 2. Abortive: Viraemia without viral replication (fever, headache and vomiting). 3. Non paralytic: Reach CNS causing stiff neck and pain. It subside or become paralytic. 4. Paralytic: Occur only in 1 % of cases where it replicate in CNS causing paralysis.  The virus is detected in feces at any time during the course of infection.  Secretory antibodies are transient but could prevent initiation of infection.  Serum antibodies block viremic spread to the target tissues.  In paralytic poliomyelitis the virus affects the anterior horn cells of the spinal cord leading to flaccid or frank paralysis.  In severe cases the posterior horn may be also affected leading to loss of sensation.  Laboratory Diagnosis: 1. Isolation of the virus on primate cells (human and monkey) and demonstration of the characteristic CPE. 2. Rise in antibody titer.  Prophylaxis:  Two types of vaccines are available, both containing the three serotypes  Sabin vaccine Salk vaccine Living attenuated vaccine Killed vaccine Oral vaccine Given by injection (IM) Replicate portal Do not replicate immunity no portal immunity Spread Herd immunity Do not spread no herd immunity Permanent Immunity 5 years long immunity Less expensive More expensive Superior but risky (living) Inferior but safe (killed)  d. Rhinoviruses  Rhinoviruses are the most important cause of common cold and upper respiratory tract infections, usually nose, infected cells release bradykinin and histamine, which cause the runny nose.  Infections are self limiting and do not cause serious disease. Continue  In contrast to enteroviruses, they are unable to replicate in the gastrointestinal tract.  Immunity to rhinoviruses is transient due to the large number of serotypes (more than 100) and being mainly secretory IgA.  They are pleomorphic (spherical or tubular), enveloped viruses.  The envelope is composed of lipid bilayer with an inner matrix M protein and outer surface 2 glycoprotein spikes {hemagglutinin (HA) and neuraminidase(NA)}, which are two important antigens.  The nucleocapsid is helical with negative sense SS RNA genome.  In case of influenza A&B the genome consists of 8 segments. Model of Influenza A virus  Antigenic variation:  It is common in influenza virus due to changes in the HA & NA. Two types of variation are demonstrated:  Antigenic drift: minor changes due to mutation and affects the severity of the disease.  Antigenic shift: major changes due to recombination between two different strains and results in new antigenic type which usually starts an epidemic or even pandemic.  Pathogenesis and clinical symptoms:  Influenza A is the most severe and C is the least. Influenza initially establishes a local upper respiratory tract infection.  The NA cleaves cialic acid residue of the mucus facilitating penetration of the virus into mucus secreting and ciliated epithelial cells and destroy them, thus facilitates adhesion of bacteria such as Pneumococci which easily then attack the respiratory- epithelia.  Secretary IgA as well as cellular immunity plays the major role in protection against this virus.  Depending on the degree of immunity, the infection range between asymptomatic and severe.  The disease starts by rapid onset fever, malaise, myalgia and nonproductive cough, sore throat, headache and is usually self limiting, however, complication with secondary bacterial infection (pneumonia), fatal anoxia may occur.  Short life immunity to influenza virus is due to: 1. Continuous variation (shift and drift) of the virus. 2. The virus rarely invades the blood, if ever. 3. The short incubation period as well as the short disease time.  Laboratory diagnosis:  Detection of rising antibody titre by hemagglutination inhibition, ELISA or RIA.  Treatment and prophylaxis:  Symptomatic treatment + antibiotic to prevent secondary infection.  Amantadine and rimantadine are effective for prophylaxis and during the first 24 hrs of infection with influenza type A.  Vitamin C and rest in bed.  Immunization with formalin killed vaccine are available each year with the suspected type A and B variants.  They are pleomorphic (spherical or tubular), enveloped viruses.  The envelope is composed of lipid bilayer and an inner matrix M protein and contains on its surface 2 glycoprotein spikes {hemagglutinin and neuraminidase on one spike (HN) and a second one of fusion protein (F)}, which are important antigens.  The nucleocapsid is helical with negative sense SS RNA one segment genome. Model of Paramyxovirus  a. Parainfluenza  It cause the following diseases: 1. Croup: by type 1& 2 (an inflammation of larynx, trachea, bronchi especially in children). 2. Bronchitis, pneumonia: by type 3 (in infants of age less than one year). 3. Mild upper respiratory tract infection ( by type 4).  Laboratory Diagnosis: as influenza  Treatment: no specific treatment. Influenza Parainfluenza  RNA Segmented (8 segments)  Non segmented  N & H on separate spikes  On one spike  No fusion antigen  Cause fusion  Show antigenic variation  Stable  Type A, B, & C  Type 1, 2, 3 & 4  Vaccine, amantadin are  No vaccine or therapy available  b. Respiratory Syncytial Virus  Infects mainly infants and children below 3 years resulting in pneumonia that may be fatal due to obstruction of narrow airways.  It causes syncytia that allow the virus to pass from cell to cell directly.  Laboratory Diagnosis: Demonstration of viral antigen in nasal washings by immunofluorescence technique.  Treatment: supportive with adequate oxygenation.  c. Mumps virus ‫النكاف‬  Mumps virus is a highly communicable disease infecting only humans (childhood disease) , with incubation period of 16-18 days.  Only one serotype exists.  It is the cause of acute benign viral parotitis (swelling of salivary parotid glands), with viraemia , ovaritis or orchitis leading to sterility in case of bilateral orchitis. Bilateral parotid and submandibular gland Lateral view showing enlargement enlargement displacing the ear lobes of salivary gland laterally Laboratory Diagnosis: Isolation of the virus from saliva, urine or CSF on monkey kidney cells. serological testing (ELISA, hemagglutination inhibition): four fold increase in antibody titer (IgG) or detection of specific IgM.  Treatment and control :  As there is no specific antiviral agent, vaccination using the MMR (living attenuated mumps-measles-rubella) vaccine is the only protective measure.  Immunity is life long following infection or vaccination.  d. Measles virus (Rubeola) ‫الحصبة‬  Measles virus is a highly communicable disease infecting mainly children , with 8-12 days incubation period.  Only one serotype exists.  0 day then Lasts for 2-4 days Lasts for 4-5 days Complications incubation period - Droplet - (3,C) cough, - Localize in skin - Pneumonia infection (local coryza, and mucus - Otitis Media replication in conjunctivitis. membranes. - Encephalitis respiratory - High fever and - Rash all over the - Subacute tract) then koplik's spots body (from face Sclerosing passes to the (pin point bluish to trunk). panencephali- lymph nodes. white ulcers - Enlargement of tis (SSPE) surrounded by cervical lymph erythema) in the nodes buccal mucosa. (lymphoadenopathy) Measles, with Koplik's spots on the buccal mucosa Measles (rubeola). generalized rash in a Measles (rubeola). generalized rash in a child with a runny nose and sore eyes child with a runny nose and sore eyes  Laboratory Diagnosis: clinically.  Treatment and control :  As there is no specific antiviral agent, vaccination using MMR vaccine is the only protective measure (is not given to immunosuppressed persons or during pregnancy).  Antibodies are formed within 2-3 weeks. Immunity is life long following infection or vaccination and is mainly cell mediated.  Symptomatic treatment + Antibiotics to prevent secondary infections.  ‫ن‬ ‫م‬ ‫ل‬ ‫ص‬‫ح‬ ‫ل‬‫ا‬ a. Rubella (German measles) ‫بة الا ا بة‬  It is one of the Toga viruses, which are icosahedral enveloped viruses with positive sense SS RNA.  Only one serotype exists. I. Postnatal rubella: Resemble measles in causing fever and skin rash , but the disease is milder with no koplik's spots and is self limiting. Rubella. A typical diffuse macular Rubella. Close up of the rash rash over the trunk II. Congenital rubella:  Rubella infection is very serious in pregnant ladies as it crosses the placenta , including abortion, still birth, & congenital defects.  The virus affects differentiation but not proliferation of the fetal cells and so it is very dangerous during the first trimester of pregnancy only.  It results in congenital defects (splenomegally, purpurea, deafness, blindness, heart defects, and mental retardness) in the fetus, specially during the first three months of pregnancy.  Laboratory Diagnosis: serological testing (ELISA, hemagglutination inhibition): four fold increase in antibody titer (IgG) or detection of specific IgM.  Treatment and control :  As there is no specific antiviral agent, vaccination using the MMR vaccine or using living attenuated single rubella vaccine before marriage for girls is the only protective measure.  Vaccination should be avoided during pregnancy and for 3 months before pregnancy.  Immunity is life long following infection or vaccination.  Rubeola Rubella Measles German measles Paramyxo Toga )- ve( SS RNA )+ ve( SS RNA Helical Icosahedral Severe course Mild course Less severe in pregnancy Severe in pregnancy Long duration Short duration Koplik's spots No Koplik's spots  They are bullet shaped, enveloped with negative sense SS RNA nucleocapsid viruses.  Rabies is a classic zoonotic infection transmitted from animals to humans {dog, cat (urban) or skunk, fox, bats...etc. (sylvatic)}.  The disease is acquired from rabid animal bite or by inhalation of dried bat's saliva. Rhabdovirus as seen by electron microscope  Clinical syndrome:  It is a fatal disease.  The incubation period varies from 8 days to 8 weeks according to the site of the bite, during which the virus replicates in muscles and connective tissue.  During the prodormal phase symptoms include fever, flu, headache, and itching at the site of the bite.  Neurological symptoms specific for rabies then appears due to ascend of the virus through sensory fibers.  It starts by excitation followed by descending paralysis showing photophobia, hydrophobia due to difficulty in swallow and respiratory paralysis, the last stages is accompanied by convulsions and coma and finally death. Schematic Representation of the Pathogenesis of Rabies Virus Infection  Laboratory Diagnosis:  Isolation and observation of the rabid animal for 2 weeks and if not catched the bitten person should be considered as potential case (clinical picture is basic tool for diagnose).  Diagnosis depends mainly on the animal, I. Detection of cytoplasmic Negri bodies in neurons (brain biopsy) of the rabid animal. However, absence of Negri bodies does not rule out rabies. II. Detection of viral antigen in neurons by immunofluorescent technique. Histological section of brain showing a Negri body.  Prophylaxis: 1. Eradication of rabid wild animals (difficult). 2. Vaccination of domestic dogs and cats.  Post exposure prophylaxis: 1. Wound washed immediately with water and soap followed by alcohol. 2. Administration of antirabies serum around the wound. 3. Intramuscular injection of antirabies serum.  Vaccination 1. Human diploid cell strain (HDCS) vaccine: chemically inactivated virus given as 5 IM at 0, 3, 7, 14, and 28 days after the bite. 2. Duck embryo vaccine (DEV): chemically inactivated virus given as 14 or better 21 doses are injected , however, it may cause hypersensitivity. C. Lentiviruses: Human immunodeficiency viruses (HIV-1 and HIV-2), causing acquired immunodeficiency syndrome (AIDS). HIV-1 was formerly known as HTLV-3.  Two serotypes are found, HIV-1 which is world wide and HIV-2 which is prevalent in west Africa and is less virulent.  Mode of transmission and risk factors:  sexual intercourse (homo and hetero), blood transfusion and blood products, drug abusers (drug addicts sharing syringes), infants from infected mother (transplacental), breast milk, organ transplantation, and contacts with high risk specimens.  HIV is not transmitted by day to day contact except sexual intercourse and there is no evidence for transmission by saliva (coughing or sneezing), insects, casual social contact or sharing eating or drinking utensils.  Pathogenesis and clinical manifestations:  The major determinant of HIV pathogenesis is its tropism to CD4 T cells and macrophages.  Early infection with HIV is usually asymptomatic which is then followed by mononucleosis with lymphadenopathy, fever, rash and sometimes aseptic meningitis.  During this phase the virus is reverse transcriped into DNA and is integrated into the host cell chromosome and so may remain latent for years in T-cells.  However, macrophages produces persistent low level of the infecting virus (shedding) during this phase.  AIDS started due to stimulation of the virus replication in the CD4 T-cells, which is said to be due to infection with DNA viruses or other microorganisms.  It progress in the following sequence: 1. Persistent generalized lymphadenopathy (PGL). 2. AIDS-related complex (ARC), showing diarrhea, fatigue and loss of weight. 3. Fully developed AIDS syndrome, due to severe depletion in CD4 T-cells (less than500/mm3). It is characterized by development of infections and malignancy such as  Opportunistic infection: e.g. candida (thrush mouth), Pneumocytosis carinii (pneumonia), cerebrospinal toxoplasmosis, cryptococcal meningitis, tuberculosis , diarrhea by enterobacteria, recurrency of DNA latent viruses e.g. HSV, VZV, EBV, and CMV infections.  Malignancies: e.g. Kaposi's sarcoma , non hodgkin's lymphoma.  AIDS related Dementia: deterioration of intellectual abilities similar to the early stages of Alzheimer's disease. Papular cutaneous Kaposi's Hodgkin's lymphoma Sarcoma Kaposi's sarcoma. Extensive Kaposi's sarcoma. brownish pigmented lesions on Multiple lesions on the the upper extremities. feet  Laboratory diagnosis:  Usually carried to identify carriers who may transmit infection to others and to initiate antiviral therapy. 1. ELISA: used for screening procedures as it is non confirmatory (false in pregnancy, malaria, & some protozoa). 2. Western blot :determines the presence of antibody to each of the viral antigens, e.g. core protein (p24). It is more confirmatory 3. Determination of CD4/CD8 ratio. Western blot  Treatment: 1. Azidothymidine (AZT), dideoxyinosine (ddI), and dideoxcytidine(ddC). They inhibit reverse transcriptase, however they are toxic. 2. Treatment of opportunistic infections.  Control: 1. Education. 2. Behavioral Change.  Hepatitis is a term indicating inflammation of the liver, may be: I. Non infectious: (catarrhal inflammation) II. Infectious: caused by bacteria, protozoa or viruses.  Several viruses causes hepatitis e.g. cytomegalovirus and hepatitis A, B and non A non B (hepatitis C&E) also delta agent (hepatitis D) exists.  Recently hepatitis G & H are identified  All are RNA viruses except HBV (DNA virus).  Non A non B because no Anti-HAV (IgM) and no HBsAg.  Hepatitis G virus (HGV) transmitted only in contaminated blood supply and is seen when HCV and HBV are detected together.  Classification Structure Hepatitis A Picorna naked icosahedral (Entero 72) + SS RNA (linear) Hepadna partly Ds DNA (circular) Hepatitis B with 3 morphologies, spherical, filamentous and Dane Flavi Viruses icosahedral Hepatitis C Hepatitis non A non B (Toga Viruses) + SS RNA (circular) Viroid like -SS RNA Hepatitis D Unclassified (NANB) (circular) RNA with hepatitis B coat Hepatitis E Calici Viruses Spherical + SS RNA (linear)  Envelope Incubation Hepatitis A Non enveloped 15-45 days (Entero 72) Hepatitis B Enveloped 45-160 days Hepatitis non A non B Hepatitis C Enveloped 15-180 days (NANB) Hepatitis D Enveloped 15-65 days Hepatitis E Non enveloped 15-50 days  Onset Risk persons Hepatitis A Abrupt (varies) Children 12-18 years (Entero 72) Insidious Hepatitis B (varies) Hemophilics, Insidious drug addicts, Hepatitis non A non B Hepatitis C (varies) homosexuals (NANB) Abrupt (varies) Hepatitis D Abrupt (varies) Hepatitis E All ages - Normal patients: mild - Pregnant ladies: severe  Severity Chronicity Hepatitis A Mild No (Entero 72) Occasionally Yes Hepatitis B severe Hepatitis C Usually Yes Hepatitis non A non B subclinical Superinfection (NANB) Hepatitis D with HBV, Yes usually severe Hepatitis E ----- No  Transmission Associated diseases Hepatitis A Oral-fecal No (Entero 72) Hepatitis B Parentral, Hepatocellular Hepatitis C Transplacental, carcinoma and Hepatitis non A non B Sexual cirrhosis (NANB) Hepatitis D Hepatitis E Oral-fecal No  Laboratory Virus diagnosis Detection ELISA & RIA Hepatitis A Symptoms and In blood and in (Entero 72) Anti HAV IgM stool in blood, saliva, Serum levels of Hepatitis B HBsAg, HBeAg and milk, vaginal secretions and anti HBc IgM semen Hepatitis non A non Hepatitis C Anti HCV and PCR In blood, vaginal B (NANB) secretions and Hepatitis D Anti HDV semen In blood and in Hepatitis E Anti HEV stool  Complications Hepatitis A Mild self limiting but some cases (Entero 72) are sever liver cirrhosis. Occasionally sever cirrhosis, Hepatitis B hepatocellular carcinoma. Usually subclinical but of bad Hepatitis non A non B Hepatitis C restoration cirrhosis, hepatocellular carcinoma. The same complications as in HBV (NANB) Hepatitis D “ only in case of sever co-infection with HBV” Fatality is high (20 %) in the 3rd Hepatitis E trimester of pregnancy.