Medical Virology (Part 1) PDF

Medical Virology (Part 1) By Dr. Amr Shaker Lecturer of Microbiology & Immunology Week Content Lecturer 1 Introduction, Classification of Viruses, Replication cycle of viruses, DNA viruses 2 DNA viruses (cont.), RNA virus...

Medical Virology (Part 1) By Dr. Amr Shaker Lecturer of Microbiology & Immunology Week Content Lecturer 1 Introduction, Classification of Viruses, Replication cycle of viruses, DNA viruses 2 DNA viruses (cont.), RNA viruses Virology Dr. Amr Shaker 3 RNA viruses (cont.) 4 Hepatitis viruses, Hemorrhagic fever viruses 5 Protozoa 1 Dr. Yomna 6 Midterm 7 Protozoa 2 Dr. Yomna 8 Cestodes 1 Parasitology Dr. Sarra Saleh 9 Cestodes 2 10 Trematodes 11 Nematodes 1 Dr. Masarra Sakr 12 Nematodes 2 Introduction  Virology Naked virus Virology is the scientific study of viruses  Submicroscopic, acellular infectious agent  Obligate intracellular parasites  Infect humans, animals, insects, plants & even bacteria  Minimally constructed of two main components: 1. A genome consisting of either RNA or DNA, but not both 2. A protein-containing structure (capsid) designed to protect the genome 3. An envelope composed of a protein-containing lipid bilayer, whose presence or absence further distinguishes one virus group from another  Classification of viruses Viruses are divided into groups based on: 1. Nucleic acid 2. Capsid 3. Envelope A. DNA viruses A. Helical A. Enveloped ds DNA ss DNA B. Non-enveloped (Naked) B. RNA viruses B. Icosahedral ds RNA ss RNA  Steps in the replication cycles of viruses Steps: A. Viral entry 1. Adsorption 2. Penetration B. Replication & protein synthesis C. Viral assembly & Release  Steps in the replication cycles of viruses A. Viral entry 1. Adsorption The initial attachment of a virus particle to a host cell involves an interaction between specific molecular structures on the virion surface (such as the glycoprotein spikes found in viral envelopes) and receptor molecules in the host cell membrane that recognize these viral structures  Steps in the replication cycles of viruses A. Viral entry 2. Penetration There are two principal mechanisms by which viruses enter animal cells: A. Receptor-mediated endocytosis B. Membrane fusion Endosome  Steps in the replication cycles of viruses B. Replication & protein synthesis A. The viral genome replicates independent from host genome B. The viral genome is integrated with host genome  C. Viral assembly & Release 1. Naked viruses 2. Enveloped viruses Release of progeny is usually a passive event resulting from the disintegration of the dying cell therefore, may be at a relatively late time after infection  Question for you? Which is more virulent: Enveloped or naked viruses ???? Naked viruses are typically more virulent than enveloped viruses Why???  Non-enveloped viruses Enveloped viruses (Naked) don’t have that extra lipid membrane contain an outer membrane that surrounds the capsid cell lysis is the most common exit during virus assembly and exit from host mode from the host cell cells, these viruses can use the host cell membrane itself to assemble their membrane, known as an envelope During this event, the viruses violate the integrity of the cell membrane, causing cell death and significant This process avoids cell lysis and helps enveloped tissue damage to the host organism viruses escape the host’s immune system  Growth curve of virus The viral growth curve is a representation of the overall change, with time, in the amount of infectious virus in a single cell that has been infected by a single virus particle The viral growth curve begins with the eclipse period, which is followed by a period of exponential growth A. Eclipse period  it represents the time elapsed from initial entry and disassembly of the parental virus to the assembly of the first progeny virion  During this period, active synthesis of virus components is occurring B. Exponential growth period  The number of progeny virus produced within the infected cell increases exponentially for a period of time, then reaches a plateau, after which no additional increase in virus yield occur  Effects of viral infection on the host cell 1. Viral infections in which no progeny virus are produced (Abortive infection) caused by: 1) a normal virus infecting cells that are lacking in enzymes, promoters, transcription factors, or other compounds required for complete viral replication 2) Infection by a defective virus of a cell that normally supports viral replication (that is, by a virus that itself has genetically lost the ability to replicate in that cell type) 3) Death of the cell as a consequence of the infection, before viral replication has been completed  Effects of viral infection on the host cell 2. Viral infections in which the host cell may be altered antigenically but is not killed, although progeny virus are released (Productive infection)  In this case, the host cell is permissive, and the infection is productive (progeny virus are released from the cell), but viral replication and release neither kills the host cell nor interferes with its ability to multiply and carry out differentiated functions The infection is therefore said to be persistent  Effects of viral infection on the host cell 3. Viral infections that result in a latent viral state in the host cell (Latent infection)  Some viral infections result in the persistence of the viral genome inside a host cell with no production of progeny virus  Such latent viruses can be reactivated months or years in the future, leading to a productive infection  Some latently infected cells contain viral genomes that are stably integrated into a host cell chromosome  Effects of viral infection on the host cell 4. Viral infections resulting in host cell death and production of progeny virus (Lytic infection)  Eliminating host cell competition for synthetic enzymes and precursor molecules increases the efficiency with which virus constituents can be synthesized DNA viruses  DNA viruses A. Enveloped B. Non-enveloped  Herpesviruses  Adenoviruses  Poxviruses  Parvoviruses ssDNA  Hepadnaviruses  Papovaviruses All are dsDNA EXCEPT Parvoviruses  A Enveloped DNA viruses  1. Herpesviruses Eight human herpesvirus species are known: Herpes simplex Types 1 & 2 (HSV 1 & 2) Varicella-zoster virus (VZV) Cytomegalovirus (CMV) Epstein-Barr virus (EBV) Human herpesviruses (Types 6, 7 and 8) All have the ability to enter a latent state following primary infection of their natural host and be reactivated at a later time  Herpes simplex Types 1 & 2 (HSV) Two serotypes of HSV: Transmission Type 1 (HSV-1): causes lesions in Direct contact with virus containing the oral cavity and facial area secretions or with lesions on mucosal or cutaneous surfaces Type 2 (HSV-2): causes infection in the genital area Type 1 (HSV-1) Type 2 (HSV-2) Pathogenesis  Kissing or  Sexual Both HSV-1 and HSV-2 multiply in epithelial saliva- intercourse cells of the mucosal surface onto which they contaminated have been inoculated fingers  Infections of newborns during passage through Resulting in production of vesicles or shallow the birth canal ulcers containing infectious virus Congenital transmission Latent infection of HSV  Herpes simplex Types 1 & 2 (HSV) Infections HSV 1 HSV 2 1. Gingivostomatitis 1. Primary genital herpes (ulcerative lesions in oral where lesions appear on the cavity) vagina, cervix, or vulva and penis 2. Herpes labialis (cold sores or fever blisters): clusters of vesicles at 2-Neonatal herpes infection the border of the lips may be transferred from mothers with genital herpes 3. Keratoconjunctivitis 4. Herpetic encephalitis  Herpes simplex infections Herpes labialis Gingivostomatitis  Herpes simplex Types 1 & 2 (HSV) Treatment 1. Acyclovir Local application (acyclovir® or zovirax ®) skin/eye ointment or creams Cortisones are highly prohibited (contraindicated) either 2. Oral acyclovir or valacyclovir tablets for adults topically or orally 3. Local anesthetic spray or gels: (BBC®, Aftmed® spray; oracure gel ®; Salivex-L® paint) 4. Analgesics and anti-inflammatory: such as Broad spectrum antibiotics are Paracetamol & NSAIDs (ibuprofen, ketoprofen or prescribed only if necessary diclofenac may be used to reduce fever) (high fever, pus) But not aspirin Reye’s syndrome: fatal disease of the liver and brain  Varicella-Zoster virus (VZV)  Biologic similarities between VZV and HSV include the fact that latency is established in sensory ganglia  Primary infections with VZV cause  Reactivation of the latent virus varicella (chickenpox) causes herpes zoster (shingles) Transmission Pathogenesis Respiratory droplets  VZV infections 1. Primary infection 2. Recurrent infection (varicella, or “chickenpox”) (herpes zoster, or “shingles”) Childhood infection Attributed to the activation of latent Incubation period: 14-21 days varicella virus in sensory nerve ganglia First, Prodrome of fever, malaise, Herpes zoster results from reactivation headache, and abdominal pain of the latent virus, not from new, (1-3 days) exogenous exposure Skin rash (Exanthem) begins on the scalp, face, or trunk as macules, which The virus moves down the sensory nerves until evolve into virus-containing vesicles it reaches the skin, where it replicates and that begin to crust over after about 48 produces localized lesions similar to those of hours (Severe itching) chickenpox Complications (6-7 days) Healing occurs without scarring Post-herpetic neuralgia Pain after the vesicles heal, frequently occurs in adults more than 60 years old  VZV infections 1. Primary infection 2. Recurrent infection (varicella, or “chickenpox”) (herpes zoster, or “shingles”)  Varicella-Zoster virus (VZV) Treatment Prophylaxis 1. Local application of calamine lotion, Zn oxide  Chickenpox (Varicella) (soothing and anti-pruritic) plus Antihistamines: vaccine protects children and adults from orally/topically chickenpox (Live-attenuated) 2. Oral/topical acyclovir is started within 24 Children need 2 doses of varicella hours of rash (children) onset vaccine, usually:  First dose: age 12 through 15 3. Analgesics, antipyretic and anti- months inflammatory: Paracetamol, NSAIDs BUT NOT  Second dose: age 4 through 6 aspirin (because of Reye syndrome) years Older children, adolescents, 4. Maintain good hygiene and daily cleaning of and adults also need 2 doses of skin with warm water to avoid secondary varicella vaccine if they are not already bacterial infection (Cutting nails or wearing immune to chickenpox. gloves)  Epstein–Barr virus (EBV) EBV is named after Michael Epstein and Yvonne Barr, who together discovered the virus in 1964 Its initial discovery in association with The first human virus clearly the childhood disease Burkitt related to a malignancy lymphoma Infection by EBV is usually established early in childhood in most parts of the world and remains silent throughout a person’s life Transmission Primarily spread through saliva (Kissing)  Epstein–Barr virus (EBV) Diseases Primary infection in infancy or childhood is usually asymptomatic About 50%of those infected, later in life develop infectious mononucleosis 1. Infectious mononucleosis 2. Malignancies (Glandular fever) (Kissing disease) Classic clinical triad of Burkitt lymphoma (BL) infectious mononucleosis Fever Pharyngitis Lymphadenopathy  Human cytomegalovirus (CMV) The infected cells typically are greatly enlarged and multinucleated Initial infection with CMV commonly occurs during (Cytomegalo-) childhood Transmission 1. Direct contact with infected body fluids  Tears, urine, and saliva (Kissing) 2. Sexual intercourse 3. Blood transfusions and organ transplants 4. Congenital transmission  Transplacentally  Perinatal (Breastfeeding)  Human cytomegalovirus (CMV) Diseases A. Infection in the B. Infectious newborn (congenital Mononucleosis CMV) Usually manifested as  Infection passed from fever, pharyngitis and pregnant women to fetus lymphocytosis The fetus becomes infected with virus leading to microcephaly, hepatosplenomegaly, & CNS infection  Diagnosis of Infectious mononucleosis (Glandular fever) A. Clinical diagnosis B. Laboratory diagnosis  For EBV (Monospot test or mononuclear spot test or Paul-Bunnell test)  For CMV (CMV-IgG and CMV-IgM)  CBC (marked lymphocytosis) C. Abdominal Ultrasonography To detect spleenomegaly  Treatment of Infectious mononucleosis (Glandular fever) 1. Analgesic and anti-inflammatory  Paracetamol, NSAIDs, (Ibuprofen, ketoprofen, diclofenac)  Avoid use of corticosteroids particularly systemic  enzymatic anti-inflammatory agents (trypsin, alpha amaylase) 2. Antiviral  Valacyclovir or acyclovir (for EBV))  CMVIgs 3. Antibiotics  To treat secondary bacterial infections such as pharyngitis and follicular tonsillitis caused by Streptococcus pyogenes  Human herpesvirus-6 (HHV-6) HHV-6 is believed to be acquired early in life and to establish a latent infection Typically, the disease affects a child between six months and two years of age Clinical manifestations Disease Begins with a sudden high fever (39–40 °C) After a few days (max. 3 days) the fever Roseola infantum subsides, and a red rash appears. This (Sixth disease)** usually begins on the trunk, spreading to the legs and neck The rash is not itchy and may last 1 to 2 days  2. Poxviruses Poxviridae is a big family of viruses, including about 83 species The most important are: 3. Vaccinia virus 1. Molluscum contagiosum virus (MCV) Is the source of the modern vaccine against water warts smallpox (Live vaccine) Is a viral infection of the skin that results in small raised pink lesions with a dimple in the center (resolve in 6-12 months) 2. Variola virus  Transmitted by inhalation of virus released from lesions,  The virus spread from oropharynx to blood stream and finally lodged in skin Smallpox Eradicated in 1977  The virus lodged in the skin produce a rash (Pustular) Vaccinia virus  The rash pustules falls down & leaves permanent scars vaccine 4. Monkeypox (Mpox) virus Transmission Signs & symptoms Human to human  Rash  Direct contact with infectious lesion  Fever material or fluid on the skin  sore throat  Sexual intercourse  headache  muscle aches Animal to human  Swollen lymph nodes bites or scratches, or during activities such as hunting, skinning, or cooking infected animals Prevention Diagnosis  Identifying mpox can be difficult because other Vaccinia virus vaccine infections and conditions can look similar (chickenpox, measles, bacterial skin infections, scabies, herpes, syphilis)  The preferred laboratory test for mpox is polymerase chain reaction (PCR) Thanks!