1 Medical virology Dr. Hala Al Daghistani

2 Viruses Non-living agents that infect all life forms (plants, phages, and animal viruses) Viral cultivation differs from bacterial cultivation Only EM allowed for visualization of viruses Viruses have one major characteristic in common: (they are obligate intracellular parasites). No virus is able to produce its own energy (ATP) to drive macromolecular synthesis.

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4 General Characteristics of VirusesContain DNA or RNA Contain a protein coat = Capsid that made up of Capsomeres (NA + capsid neucleocapsid). Some are enclosed by an Envelope (Naked , Enveloped) Some viruses have Spikes (COH/protein) Most viruses are tissue specific Host range is determined by specific host attachment sites and cellular factors

5 Morphology of an enveloped helical virus

6 ICAM-1(intracellular adhesion molecule 1 present on WBC, endothelium) RECEPTOR VIRUS ICAM-1(intracellular adhesion molecule 1 present on WBC, endothelium) Polio CD4 HIV Acetylcholine (neural impulse transduction) Rabies EGF (epidermal growth factor) Vaccinia CR2/CD21(complement receptors) Epstein-Barr HVEM (herpesvirus entry mediator) Herpes Sialic acid(common component of extracellular glycosylated proteins, surface cells) Influenza, corona

7 Host Range and SpecificityVirus and host cell interaction usually very specific (narrow host range) Specific Tissue tropism  is the cells and tissues of a host which support growth of a particular virus . -Some bacteria and viruses have a Broad tissue tropism and can infect many types of cells and tissues. For example rabies virus affects primarily neuronal tissue. Doc Kaiser's Microbiology Home Page Copyright © Gary E. Kaiser All Rights Reserved Updated: March 15, 2001

8 Virus Shapes and Sizes

9 Structural Classes Icosahedral symmetry Helical symmetryNon enveloped (“naked”) Enveloped

10 Icosahedral capsids a) Crystallographic structure of a simple icosahedral virus. b) The axes of symmetry

11 Helical symmetry In 1955, Fraenkel, Conrat, and Williams demonstrated that tobacco mosaic virus (TMV) spontaneously formed when mixtures of purified coat protein and its genomic RNA were incubated together. The structure that TMV adopts is self-ordered and corresponds to a free energy minimum. This was and remains a remarkable discovery. TMV, a filamentous virus

12 Enveloped helical virusEnveloped icosahedral virus

13 Satillite virus Virons (viruse) Viroids Prions Contain nucleic acidDepend on co-infection (simultaneously) with a helper virus or superinfection (carrier, chronic) Mostly in plants, can be human e.g. Hepatitis delta virus (HDV), cannot propagate without HBV Viroids Unencapsidated, small circular ssRNA molecules that replicate autonomously Only in plants, e.g. potato spindle tuber viroid Prions No nucleic acid Infectious protein e.g. BSE(bovine spongiform encephalopathy or mad cow disease) Virons (viruse) A complete viral particle, consisting of RNA or DNA surrounded    by a protein shell and constituting the infective form of a virus.

14 Principle of viral infectionsAll viruses package their genomes inside a particle that mediates transmission of the viral genome from host to host The viral genome contains the informations for initiating and completing an infectious cycle within a susceptible, permissive cell. An infectious cycle includes attachment, and entry of the particle, uncoating, transcription and or translation of viral genome, replication, and assembly and release of particles containing the genome

15 Typical infectious cycle

16 Attachment(Adsorption)Virus encounters susceptible host cells Adsorbs specifically to receptor sites on the cell membrane Because of the exact fit required, viruses have a limited host range

17 Figure 6.12

18 Penetration UncoatingFlexible cell membrane of the host is penetrated by the whole virus or its nucleic acid Endocytosis: entire virus engulfed by the cell and enclosed in a vacuole or vesicle The viral envelope can also directly fuse with the host cell membrane Uncoating Enzymes in the vacuole dissolve the envelope and capsid The virus is now uncoated

19 Synthesis Free viral nucleic acid exerts control over the host’s synthetic and metabolic machinery DNA viruses- enter host cell’s nucleus where they are replicated and assembled DNA enters the nucleus and is transcribed into RNA The RNA becomes a message for synthesizing viral proteins (translation) New DNA is synthesized using host nucleotides RNA viruses- replicated and assembled in the cytoplasm Assembly Mature virus particles are constructed from the growing pool of parts

20 Release Nonenveloped and complex viruses are released when the cell lyses or ruptures Enveloped viruses are liberated by budding or exocytosis Anywhere from 3,000 to 100,000 virions may be released, depending on the virus Entire length of cycle- anywhere from 8 to 36 hours

21 Attachment, Penetration, and UncoatingFigure 13.14

22 Viral Replication Obligate intracellular parasites using host cell machinery Very limited number of genes encode proteins for Capsid formation Viral nucleic acid replication Movement of virus into and out of cell Kill or live in harmony within the host cell Outside the cell, viruses are inert

23 How are viruses named? Based on: 1- the disease they causepoliovirus, rabies virus 2- the type of disease murine leukemia virus 3- geographic locations Sendai virus, Coxsackie virus 4- their discovers Epstein-Barr virus 5- how they were originally thought to be contracted dengue virus (“evil spirit of Babylonia”) cramp-like seizure, influenza virus (the “influence” of bad air) 6- combinations of the above Rous Sarcoma virus

24 Taxonomy of Viruses Family names end in –viridaeNo evidence for common viral ancestor. Taxonomy from Order downward (3 orders now recognized) Classification based on type of NA, strategy for replication, and morphology. Family names end in –viridae Many families have subfamilies. Ends in -virinae. Genus and species names end in -virus. Viral species: A group of viruses sharing the same genetic information and ecological niche (host). Common names are used for species. Subspecies are designated by a number.

25 Taxonomy of Viruses Retroviralis(order) Herpesviralis(order)Herpesviridae (family) Herpesvirus (genus) Human herpes virus (species) HHV-1, HHV-2, HHV-3 (subspecies) Retroviralis(order) Retroviridae(family) Lentivirus (genus) Human immunodeficiency virus (species) HIV-1, HIV-2(subspecies)

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27 The Baltimore classification systemBased on genetic contents and replication strategies of viruses. According to the Baltimore classification, viruses are divided into the following seven classes: 1. dsDNA viruses 2. ssDNA viruses 3. dsRNA viruses 4. (+) sense ssRNA viruses (codes directly for protein) 5. (-) sense ssRNA viruses 6. RNA reverse transcribing viruses 7. DNA reverse transcribing viruses. where "ds" represents "double strand" and "ss" denotes "single strand". All viruses must produce mRNA, or (+) sense RNA The Baltimore classification has + RNA as its central point

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29 - Most genomes are non-segmented (the genome is all on one piece of RNA or DNA). - Some genomes are segmented, meaning there are several fragments of genetic material that make a complete virus genome. - Also, some genomes are linear, meaning that there is a beginning and end to the genome, while other genomes are circular (no beginning and no end|).

30 Isolation, Cultivation, and Identification of VirusesFig 13.6 Viruses must be grown in living cells Bacteriophages form plaques on a lawn of bacteria Animal viruses may be grown in cell culture, embryonated eggs, or living animals

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32 Using Cell (Tissue) Culture TechniquesMost viruses are propagated in some sort of cell culture The cultures must be developed and maintained Animal cell cultures are grown in sterile chambers with special media Cultured cells grow in the form of a monolayer Primary or continuous

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34 Virus Identification Cytopathic effects Serological testsIdentify antibodies against viruses in a patient Use antibodies to identify viruses in neutralization tests, viral hemagglutination Nucleic acids PCR

35 Anti-Viral Drugs Attachment antagonists Inhibit UncoatingBlock attachment molecule Arildone Inhibit Uncoating Neutralize acid environment Amantadine Rimantadine Inhibit DNA/RNA synthesis Activation by phosphorylation of drug by viral kinases Acyclovir Gancyclovir

36 Bacteriophage: The Lytic CycleAttachment to cell surface receptors - no active movement) Penetration – only genome enters Biosynthesis – Production of phage DNA and proteins Maturation – assembly to form intact phage Release due to phage induced lysozyme production See Fig 13.11

37 Lytic Cycle of Bacteriophage1 2 3 Fig 13.11

38 Lytic Cycle of a T-Even Bacteriophage4 Fig 13.11

39 Results of Multiplication of BacteriophagesLytic cycle Lytic or virulent phage Phage causes lysis and death of host cell Lysogenic cycle Lysogenic or temperate phage Phage DNA incorporated in host DNA  Prophage Phage conversion

40 Lytic and Lysogenic CyclesFig 13.12

41 Viral Pathogenesis: Elements of Virus-Host InteractionViral strain Inoculum size Route of exposure Susceptibility of host Is there pre-existent immunity from past exposure or vaccination? Host genetic factors Immune status and age of host

42 Pathogenetic Steps in Human Viral InfectionVirus may enter through skin, mucous membranes, respiratory tract, GI tract, via transfusion, needle-stick, or maternal-fetal transmission Local replication at site of inoculation Neurotropic agents may travel along nerve routes or reach CNS by viremic spread

43 Pathogenetic Steps in Human Viral InfectionFor many agents, there is replication in regional lymph nodes with subsequent viremia and spread to target organs Some travel free in plasma (e.g., picornaviruses); some are cell associated (e.g., cytomegalovirus) Replication in target organs may lead to local damage and further viremia Non-specific and virus-specific host immune responses come into play to downregulate viral replication

44 Immune Response to Viral InfectionsNon-specific immunity Phagocytic cells (neutrophils and monocyte-macrophages) Cytokines (e.g., interferons) Natural killer cells Other ‘antiviral’ factors Specific immunity Antigen specific B and T cell responses Antibodies Cytotoxic T cells ADCC

45 Immune Response

46 18 GROUPS ( 6 are DNA VIRUSES, 11 are RNA VIRUSES and 1 UNCLASSIFIED)VIRAL TAXONOMY 18 GROUPS ( 6 are DNA VIRUSES, 11 are RNA VIRUSES and 1 UNCLASSIFIED) DNA VIRUSES 1. Poxvirus (1) the largest viruses (2) enveloped double stranded DNA viruses (3) intracytoplasmic inclusion bodies (4) skin is a primary target (5) eg. smallpox, cowpox 2. Herpesvirus (1) medium size (2) enveloped Double-stranded DNA viruses (3) intranuclear inclusion bodies (4) skin is the major target. (5) eg. Epstein Bar viruses

47 (2) Double stranded DNA viruses 3. Adenoviurs (1) medium size (2) Double stranded DNA viruses (3) non-enveloped, intranuclear inclusion bodies (4) target: human lymphoid tissue. (5) eg. tumors in animals 4. Papovavirus (1) small size (2) non-enveloped double stranded DNA (3) tumor producing viruses (4) eg. papilloma virus of human, polyoma viruses of mice.

48 5. Parvovirus (1) ultra small in size (2) single stranded DNA viruses (3) among the most resistant viruses known. (4) eg. human parvovirus B19 or fifth disease 6. Hepadnavirus (1) enveloped DNA virus, Double stranded DNA (2) replication in liver cell (3) eg. hepatitis B

49 7. Myxovirus (Orthomyxoviruses) (1) medium size RNA VIRUSES 7. Myxovirus (Orthomyxoviruses) (1) medium size (2) enveloped single stranded RNA virus with helical symmetry (3) many can agglutinate red blood cells (4) eg. influenza viruses cause flu 8. Paramyxovirus (2) enveloped single stranded RNA viruses helical symmetry (3) both intracytoplasmic and intranuclear inclusion bodies (4) eg. measles, mumps

50 *9. Rhabdovirus (1) medium size (2) single stranded RNA viruses, helical symmetry (3) bullet shaped envelop (4) intracytoplasmic inclusions (5) transmitted by animal or animal bites (6) eg. vesicular stomatitis, rabies *10. Flavivirus (1) small size (2) enveloped single stranded RNA viruses (3) transmitted by mosquitoes or ticks (4) eg. yellow fever, Dengue viruses, Japanese Encephalitis

51 (2) enveloped single stranded RNA viruses 11. Togaviruses (1) small size (2) enveloped single stranded RNA viruses (3) complex life cycle involving biting insects (4) eg. Dengue like fever. 12. Arenavirus (1) medium size (3) transmitted by animal or animal bites (4) eg. South American hemorrhagic fever 13. Bunyavirus (3) arthropod-borne viruses, transmitted by mosquitoes or ticks (4) eg. California encephalitis

52 14. Reovirus (1) medium size (2) Double stranded RNA viruses (3) transmitted by mosquitoes or ticks (4) in respiratory tract, enteric canal. (5) eg. infantile gastroenteritis 15. Picornavirus (1) smallest viruses (2) single stranded RNA viruses (3) enteric and related virus (4) eg. poliomyelitis, common cold. 16. Coronavirus (2) single stranded enveloped virus (helical symmetry) (3) eg. Avian infectious bronchitis

53 17. Retrovirus (1) small size (2) enveloped single stranded RNA tumor virus (3) has reverse transcriptase (4) eg. leukemia or sarcoma in mice, AIDS 18. Other viruses (1) unclassified (2) eg. some slow neurologic disorders.

54 The Effect of Virus Infection on the Host CellCytopathic Effects 2. Inhibition of Host Macromolecular Biosynthesis 3. Changes in the Regulation of Gene Expression 4. Appearance of New Antigenic Determinants on the Cell Surface (If it is enveloped virus, the new determinants are likely to be viral envelope proteins. It can also be non enveloped virus. The presence of these determinants serves to alert the immune mechanism). 5. Cell Fusion(the formation of giant syncytia, mass of cytoplasm bounded by one membrane that contain hundreds and even thousands of nuclei.

55 6. Abortive Infection (viral infection that infects a cell without reproducing into more infectious viruses. This occur when a virus infects a cell, but cannot complete the full replication cycle 7. Persistent Infection with Latency (Persistent infection with no viral progeny.  Latency is the phase that occur after initial infection and proliferation of virus. However, the viral genome is not fully eradicated. The result of this is that the virus can reactivate and begin producing large amounts of viral progeny without the host being infected by new outside virus.

56 RNA Viruses

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58 Insert Table 25.1 RNA viruses

59 Orthomyxoviruses: InfluenzassRNA, segmented, consists of 10 genes encoded on 8 separate RNA segments. 3 distinct influenza virus types: A, B, C; Type A causes most infections Influenza A viruses are further classified, based on the viral surface proteins hemagglutinin (HA or H) and neuraminidase (NA or N) Key to influenza virus are Influenza virus A infects humans, other mammals, birds, and causes all flu pandemics (H1N1, H1N2, H2N2, H3N1, H5N1, ......) Influenza virus B infects humans and seals Influenza virus C infects humans, pigs, and dogs. Virus attaches to, and multiplies in, the cells of the respiratory tract, assembled and budded off.

60 hemagglutinin (H) – 16 different subtypes; most important virulence factor; binds to host cellsneuraminidase (N) – 9 subtypes – hydrolyzes mucus and assists viral budding and release Both glycoproteins frequently undergo genetic changes decreasing the effectiveness of the host immune response. Influenza B :Not known to undergo antigenic shift Influenza C: Known to cause only minor respiratory disease; probably not involved in epidemics

61 Influenza A Acute, highly contagious respiratory illnessRespiratory transmission Binds to ciliated cells of respiratory mucosa Fever, headache, myalgia, pharyngeal pain, shortness of breath, coughing Weakened host defenses predispose patients to secondary bacterial infections, especially pneumonia.

62 Diagnosis, Treatment, PreventionRapid immunofluorescence tests to detect antigens in a pharyngeal specimen. Treatment: control symptoms; amantadine, rimantadine, zanamivir (Relenza) and oseltamivir (Tamiflu) Flu virus has developed high rate of resistance to amantadine and rimantadine. Annual trivalent vaccine recommended

63 Paramyxoviruses Paramyxoviruses Including the following virusesParainfluenza Mumps virus Morbillivirus (measles virus) Pnuemonovirus (respiratory syncytia virus) Respiratory transmission Envelope has HN and specialized F spikes that initiate cell-to-cell fusion. Fusion with neighboring cells – syncytium or multinucleate giant cells form

64 Effects of paramyxovirusesInsert figure 25.5 Effects of paramyxoviruses

65 Parainfluenza Widespread as influenza but more benignRespiratory transmission Seen mostly in children Minor cold, bronchitis, bronchopneumonia, croup No specific treatment available; supportive therapy

66 Mumps Epidemic parotitis; self-limited, associated with painful swelling of parotid salivary glands Humans are the only reservoir. 40% of infections are subclinical; long-term immunity. Incubation 2-3 weeks fever, muscle pain and malaise, classic swelling of one or both cheeks Usually uncomplicated invasion of other organs; in 20-30% of infected adult males, epididymis and testes become infected; sterility is suspected Live attenuated vaccine MMR

67 Measles Caused by Morbillivirus Also known as red measles and rubeolaDifferent from German measles Very contagious; transmitted by respiratory aerosols Humans are the only reservoir. Sore throat, dry cough, headache, conjunctivitis, lymphadenitis, fever, Koplik spots – oral lesions Exanthem Most serious complication is subacute sclerosing panencephalitis (SSPE), a progressive neurological degeneration of the cerebral cortex, white matter and brain stem. Attenuated viral vaccine MMR

69 Rhabdovirus : Rabies Rabies virus Enveloped, bullet-shaped virionsSlow, progressive zoonotic disease Primary reservoirs are wild mammals; it can be spread by both wild and domestic mammals by bites, scratches, and inhalation of droplets. Virus enters through bite, grows at trauma site and multiplies, then enters nerve endings and advances toward the ganglia, spinal cord and brain. Clinical phases of rabies: Prodromal phase – fever, nausea, vomiting, headache, fatigue; some experience pain, burning, tingling sensations at site of wound Furious phase – agitation, disorientation, seizures, hydrophobia Dumb phase – paralyzed, disoriented, progress to coma phase, death

70 Structure of rabies virusInsert figure 25.8 Structure of rabies virus

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72 Often diagnosed at autopsy – intracellular inclusions (Negri bodies) in nervous tissuePreventive therapy initiated if signs of rabies appear Treatment – infuse the wound with human rabies immune globulin (HRIG) ; vaccination with an inactivated vaccine given in 6 doses. Control - vaccination of domestic animals, elimination of strays, and strict quarantine practices

73 Coronaviruses Relatively large RNA virusesDistinctively spaced spikes on their envelopes Common in domesticated animals Coronaviruses are species in the genera   belonging to one of two subfamilies : Coronavirinae and Torovirinae . Coronaviruses primarily infect the URT and GIT of mammals and birds. Six different strains of coronaviruses infect humans. The most important human coronavirus, SARS-CoV which causes SARS (Severe Acute Respiratory Syndrome ) associated with both URT and LRT infections. It is a serious form of pneumonia SARS is an airborne disease with 10% fatality. The virus is extremely contagious. It is able to survive several hours outside human body which increase the probability of someone becoming infected through a common object.

74 Rubellavirus(Togaviruses)Caused by a Togavirus, ssRNA causative agent of German measles Most cases reported are adolescents and young adults. Transmitted through contact with respiratory secretions. A rash may start around two weeks after exposure and last for three days. It usually starts on the face and spreads to the rest of the body. The rash is not as bright as that of measles and is sometimes itchy. Swollen lymph nodes are common and may last a few weeks. A fever, sore throat, and fatigue may also occur. In adults joint pain is common. Complications may include bleeding problems, testicular swelling, and inflammation of nerves. Congenital rubella – infection during 1st trimester most likely to induce miscarriage or multiple defects such as cardiac abnormalities, ocular lesions, deafness, mental and physical retardation

76 Flavivirus (Flaviviridae)Hepatitis C Virus (HCV), non-A non-B virus Acquired through blood contact – blood transfusions, needle sharing by drug abusers Possible to have severe symptoms without permanent liver damage; more common to have chronic liver disease Cancer may also result from chronic HCV infection. Treatment with interferon and ribavirin to lessen liver damage No vaccine

77 Retroviruses HIV Infections and AIDSHuman immunodeficiency virus or AIDS, First emerged in 1980s HIV-1 may have originated from a chimpanzee virus. Encode reverse transcriptase enzyme which makes a double stranded DNA from the single-stranded RNA genome Viral genes permanently integrated into host DNA HIV can only infect host cells that have the required CD4 marker plus a coreceptor. Transmission occurs by direct and specific routes: mainly through sexual intercourse and transfer of blood or blood products; babies can be infected before or during birth, and from breast feeding. HIV does not survive long outside of the body. Men account for 70% of new infections. In 2006, the number of infected individuals worldwide is estimated to be 45 million with ~1 million in the U.S.

78 Insert figure 25.13 HIV general structure

79 Pathogenesis and Virulence Factors of HIVHIV enters through mucous membrane or skin and travels to dendritic phagocytes beneath the epithelium, multiplies and is shed. Virus is taken up and amplified by macrophages in the skin, lymph organs, bone marrow, and blood. HIV attaches to CD4 and coreceptor; HIV fuses with cell membrane. Reverse transcriptase makes a DNA copy of RNA. Viral DNA is integrated into host chromosome (provirus). Can produce a lytic infection or remain latent

80 Insert figure 25.16 Multiplication of HIV

81 Primary effects of HIV infection:extreme leukopenia – lymphocytes in particular formation of giant T cells and other syncytia allowing the virus to spread directly from cell to cell Infected macrophages release the virus in central nervous system. Secondary effects of HIV: Destruction on CD4 lymphocytes allows for opportunistic infections and malignancies.

82 Signs and Symptoms of HIV Infections and AIDSSymptoms of HIV are directly related to viral blood level and level of T cells. Asymptomatic phase 2-15 years (avg. 10) Antibodies are detectable 8-16 weeks after infection. HIV destroys the immune system. When T4 cell levels fall below 200/mL AIDS symptoms appear including fever, swollen lymph nodes, diarrhea, weight loss, neurological symptoms, opportunistic infections and cancers.

83 They fulfill one of the additional criteria:Diagnosis of AIDS is made when a person meets the criteria: Positive for the virus They fulfill one of the additional criteria: They have a CD4 count of fewer than 200 cells/ml of blood. Their CD4 cells account for fewer than14% of all lymphocytes. They experience one or more of a CDC-provided list of AIDS-defining illnesses.

84 Preventing and Treating HIVNo vaccine available No cure; therapies slow down the progress of the disease or diminish the symptoms inhibit viral enzymes: reverse transcriptase, protease, integrase inhibit fusion inhibit viral translation

85 Nonenveloped Nonsegmented ssRNA Viruses PICORNAVIRUSES Picornaviruses represent a very large virus family with respect to the number but one of the smallest in terms of virion size and genetic complexity. they include two major groups of human pathogens: 1. Enteroviruses (POLIO VIRUS) 2. Rhinoviruses . * Enteroviruses are transient inhabitants of the human alimentary tract and may be isolated from the throat or lower intestine. * Rhinoviruses are isolated chiefly from the nose and throat. Human rhinoviruses can be divided into major and minor receptor groups. viruses of the major group use intercellular adhesion molecule-1 (ICAM-1) as receptor, expressed on endothelial cells and cells of the immune system and those of the minor group bind members of the low-density lipoprotein receptor (LDLR) family, found in the plasma membrane of cells involved in receptor-mediated endocytosis..

86 Picornaviruses Poliovirus and PoliomyelitisPoliomyelitis (polio) – acute enteroviral infection of the spinal cord that can cause neuromuscular paralysis Poliovirus – naked capsid; resistant to acid, bile, and detergents; can survive stomach acids when ingested Worldwide vaccination programs have reduced the number of cases; eradication is expected.

87 Picornavirus structureInsert figure 25.22 Picornavirus structure

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89 Transmitted by fecal-oral routePolioviruses adhere to receptors of mucosal cells in oropharynx and intestine, multiply in number and shed in throat and feces, some leak into blood. Most infections are short-term, mild viremia. Most infections are subclinical; only about 1% of infections result in clinical illness. The incubation period is usually 7–14 days, but it may range from 3 to 35 days. Polio virus destroys the motor neurons in the gray matter of the spinal cord or the brain Invasion of motor neurons causes paralysis.

90 The disease could be either: AThe disease could be either: A. Mild disease This is the most common form of disease. Patient has only a minor illness, characterized by fever, malaise, drowsiness, headache, nausea, vomiting, constipation, and sore throat in various combinations. Recovery occurs in a few days. B. Nonparalytic poliomyelitis (aseptic meningitis) Patient with the nonparalytic form has stiffness and pain in the back and neck. Recovery is rapid and complete. Poliovirus is one of many viruses that produce aseptic meningitis. C. Paralytic poliomyelitis The predominating complaint is flaccid paralysis resulting from lower motor neuron damage. D. Progressive postpoliomyelitis muscle atrophy A recrudescence of paralysis and muscle wasting. Although progressive postpoliomyelitis muscle atrophy is rare.

91 Treatment and PreventionTreatment is largely supportive for pain and suffering; respiratory failure may require artificial ventilation; physical therapy may be needed. Prevention by vaccination. Injected Inactivated (killed) polio vaccine (IPV) Salk vaccine Oral live attenuated polio vaccine (OPV) Sabin vaccine Worldwide eradication anticipated by 2008

92 Hepatitis A Virus and Infectious HepatitisCubical picornavirus relatively resistant to heat and acid Not carried chronically, principal reservoirs are asymptomatic, short-term carriers or people with clinical disease Fecal-oral transmission; multiplies in small intestine and enters the blood and is carried to the liver Most infections subclinical , flu-like symptoms occur; jaundice is present Only one serotype is known. No antigenic cross-reactivity with HBV or with the other hepatitis viruses. No specific treatment once the symptoms begin Inactivated and attenuated viral vaccine Pooled immune serum globulin for those entering into endemic areas

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95 Segmented, ds RNA genome, Nonenveloped Reoviruses, Rotaviruses, and CalicivirusesUnusual double-stranded RNA genome include the following: Rotavirus – oral-fecal transmission; primary viral cause of mortality and morbidity resulting from diarrhea in infants and children. treatment with rehydration and electrolyte replacement Reovirus – cold-like URT infection, enteritis Caliciviruses are small viruses. The family contains noroviruses, the major cause of nonbacterial epidemic gastroenteritis worldwide.

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98 Double-stranded DNA, nonenveloped viruses- All of the human adenoviruses are classified in the Mastadenovirus genus. Human adenoviruses are divided into six groups (A–F) on the basis of their genetic, physical, chemical, and biologic properties Adenoviruses are cytopathic for human cell cultures, particularly kidney and epithelial cells. - The cytopathic effect usually consists of marked rounding, enlargement, and aggregation of affected cells into grapelike clusters. Mastadenovirus Respiratory infections in humans Tumors in animals

101 Ds DNA, Enveloped, HerpesvirusThe herpesviruses that commonly infect humans include: Herpes simplex virus types 1 and 2 (HSV-1, HSV-2). HSV-1 infections involved Oropharyngeal and may occur in the eye, producing severe keratoconjunctivitis, Encephalitis. Genital disease is usually caused by HSV-2, although HSV-1 can also cause clinical episodes of genital herpes Varicellazoster virus (HHV 3) Epstein-Barr virus (EBV, HHV 4). It is best known as the cause of infectious mononucleosis (glandular fever). Infection occurs by the oral transfer with saliva and genital secretions. Cytomegalovirus (CMV, HHV 5) Herpesviruses 6 and 7. HHV-6 infects T lymphocytes. It is typically acquired in early infancy and causes exanthem subitum (roseola infantum). HHV-7, also a T-lymphotropic virus, has not yet been linked to any specific disease. Herpesvirus 8 (Kaposi sarcoma-associated herpesvirus (KSHV, HHV 8). There are nearly 100 viruses of the herpes group that infect many different animal species

104 Chickenpox (VZV or HHV-3)Varicella–zoster or human herpes virus 3 of Hepesviridae family Respiratory transmission  to blood  to skin ( to sensory neuron) Macule to papule to vesicle to pustule in 24 h Pruritic (itchy) lesions – scratching may lead to serious 2 infections (S. pyogenes and S. aureus) Complications: encephalitis and Reye’s syndrome. After chickenpox, virus can remain latent in nerve cells. Reactivation later  shingles = Herpes zoster (characteristic vesicular rash along affected cutaneous sensory nerves.) A macule is a small, flat, distinct, colored area of skin that is less than 10 millimeters in diameter, and does not include a change in skin texture or thickness. A papule is a skin lesion that is small, solid, and raised. Reye's syndrome (RS) is primarily a children's disease, although it can occur at any age. It affects all organs of the body but is most harmful to the brain and the liver--causing an acute increase of pressure within the brain and, often, massive accumulations of fat in the liver and other organs. RS is defined as a two-phase illness because it generally occurs in conjunction with a previous viral infection, such as the flu or chicken pox. The disorder commonly occurs during recovery from a viral infection, although it can also develop 3 to 5 days after the onset of the viral illness. RS is often misdiagnosed as encephalitis, meningitis, diabetes, drug overdose, poisoning, sudden infant death syndrome, or psychiatric illness. Symptoms of RS include persistent or recurrent vomiting, listlessness, personality changes such as irritability or combativeness, disorientation or confusion, delirium, convulsions, and loss of consciousness. If these symptoms are present during or soon after a viral illness, medical attention should be sought immediately. The symptoms of RS in infants do not follow a typical pattern; for example, vomiting does not always occur. The cause of RS remains a mystery. However studies have shown that using aspirin or salicylate-containing medications to treat viral illnesses increases the risk of developing RS.

107 Hepadnaviridae Double-stranded DNA, enveloped virusesHepadnavirus (Hepatitis B virus) Use reverse transcriptase to produce DNA from mRNA

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111 Parvoviruses: simplest DNA animal virusesParvoviruses: simplest DNA animal viruses. - Because of the small coding capacity of their genome, viral replication is dependent on functions supplied by replicating host cells or by coinfecting helper viruses. - Parvovirus B19 is pathogenic for humans and has a tropism for erythroid progenitor cells. - it is the cause of erythema infectiosum, (“fifth disease”), a common childhood exanthem - polyarthralgia-arthritis syndrome in normal adults - Chronic anemia in immunocompromised individuals, Fetal death.

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114 Oncogenic DNA Viruses and RNA VirusesHepatitis C virus (HCV)  liver cancer human T-cell leukemia virus (HTLV-1) Papilloma virus (HPV)  cervical cancer Epstein-Barr virus (EBV)  Burkitt’s lymphoma HV8  Kaposi’s sarcoma Hepatitis B virus (HBV)  liver cancer HPV includes more than 100 different strains or types. More than 30 of these viruses are sexually transmitted, and they can infect the genital area of men and women including the skin of the penis, vulva (area outside the vagina), or anus, and the linings of the vagina, cervix, or rectum. Most people who become infected with HPV will not have any symptoms and will clear the infection on their own.    In June 2006, the Advisory Committee on Immunization Practices (ACIP) voted to recommend the first vaccine developed to prevent cervical cancer and other diseases in females caused by certain types of genital human papillomavirus (HPV). The vaccine, Gardasil®, protects against four HPV types, which together cause 70% of cervical cancers and 90% of genital warts. The Food and Drug Administration (FDA) recently licensed this vaccine for use in girls/women, ages 9-26 years. The vaccine is given through a series of three shots over a six-month period. A sarcoma is a cancer that develops in connective tissues such as cartilage, bone, fat, muscle, blood vessels, or fibrous tissues (related to tendons or ligaments). Kaposi sarcoma (KS) was named for Dr. Moritz Kaposi who first described it in 1872.