Introduction to Viruses: Viral Classification, Structure, Replication PDF

INTRODUCTION TO VIRUSES: VIRAL CLASSIFICATION, STRUCTURE, REPLICATION FACILITATOR: DR. SANCHEZ VIRUSES IN HUMAN INFECTIONS AND DISEASES  Viruses are obligate intracellular parasites  Viruses cannot make energy or proteins independently of a host cell  Viruses must be able to use host cell proce...

INTRODUCTION TO VIRUSES: VIRAL CLASSIFICATION, STRUCTURE, REPLICATION FACILITATOR: DR. SANCHEZ VIRUSES IN HUMAN INFECTIONS AND DISEASES  Viruses are obligate intracellular parasites  Viruses cannot make energy or proteins independently of a host cell  Viruses must be able to use host cell processes to produce their components (viral messenger RNA, protein, and identical copies of the genome)  Viruses must encode any required processes not provided by the cell  Reproduction of viruses occurs by assembly of the individual components rather than by sexual or asexual reproduction/division  Viruses are composed of either DNA or RNA  All DNA viruses are double-stranded except for parvoviruses, which have ssDNA  All RNA viruses are single-stranded except for dsRNA reoviruses  Viruses must be infectious to endure in nature DNA VIRUSES (1 OF 2) Virus Skin/Skeletal Nervous/Muscle Cardiovascular/L ymphatic/ Systemic Variola Virus Smallpox Molluscum contagiosum Virus Molluscum contagiosum Herpes Simplex Virus (HSV) 1 and 2 1. Oral herpes 2. Whitlows 3. Keratitis Encephalitis Varicella-Zoster Virus (VZV) Chicken pox Shingles Cytomegalovirus (CMV) Salivary glands CMV infection Epstein-Barr virus (EBV) Oral cavity, glands Infectious mononucleosis Gastrointestinal Respiratory Urogenital Viremia Genital molluscum Genital herpes DNA VIRUSES (2 OF 2) Virus Skin/Skeletal Human Herpesvirus (HHV) 6 and 7 Roseola Hepatitis B virus (HBV) Jaundice Adenovirus Conjuctivitis Human Papillomavirus (HPV) Warts Cardiovascular/ Lymphatic/ Systemic Erythema infectiosum (fifth disease) Gastrointestinal Respiratory Urogenital Hepatitis Colds Genital warts Progressive multifocal leukoencephalopathy JC virus Parvovirus B19 Nervous/Muscle Red blood cell damage RNA VIRUSES (1 OF 2) Virus Skin / Skeletal Nervous / Muscle Cardiovascular / Lymphatic / Systemic Gastrointestinal Respiratory Influenza Virus Influenza Hantavirus Hantavirus pulmonary syndrome Parainfluenza Virus Croup Mumps Virus Morbillivirus Mumps Measles Subacute sclerosing panencephalitis Respiratory Syncytial Virus (RSV) RSV disease Rabies Virus Rabies SARS-Associated Coronavirus, MERSAssociated Coronavirus Severe respiratory distress (SARS, MERS) Rubivirus Rubella Hepatitis C Virus (HCV) Jaundice Hepatitis Urogenital RNA VIRUSES (2 OF 2) Virus Skin / Skeletal Nervous / Muscle St. Louis Encephalitis Virus Encephalitis Yellow Fever Virus Yellow fever Dengue Fever Virus Dengue fever Human Immunodeficiency Virus (HIV) 1 and 2 Poliovirus Cardiovascular / Lymphatic / Systemic Gastrointestinal Yellow fever Dengue hemorrhagic fever HIV infection and AIDS Poliomyelitis Enteric infection Hepatitis A virus Hepatitis Rhinovirus Common cold Norovirus Acute diarrhea Rotavirus Acute diarrhea Ebola Virus Respiratory Ebola hemorrhagic fever Urogenital VIRAL STRUCTURES EXAMPLES EXAMPLES VIRAL REPLICATION  The major steps in viral replication are the same for all viruses  Viruses are limited to a particular host (host range) or cell type (cellular tropism)  Many viruses are strictly human in origin, others are zoonoses transmitted by vectors  Viral infections range from asymptomatic to mild to life-threatening  Common manifestations: rashes, fever, muscle aches, respiratory involvement, swollen lymph nodes  Most DNA viruses multiply within and are budded off the nucleus (except Poxviruses)  Most RNA viruses multiply in and are released from the cytoplasm (except Orthomyxoviruses and Retroviruses) PROPERTIES OF DNA VIRUSES  DNA is not transient or labile.  Many DNA viruses establish persistent infections (e.g., latent, immortalizing).  DNA genomes reside in the nucleus (except for poxviruses).  Viral DNA resembles host DNA for transcription and replication.  Viral genes must interact with host transcriptional machinery (except for poxviruses).  Viral gene transcription is temporally regulated.  Early genes encode DNA-binding proteins and enzymes.  Late genes encode structural and other proteins.  DNA polymerases require a primer to replicate the viral genome.  The larger DNA viruses encode means to promote efficient replication of their genome. EXAMPLES  Parvovirus: requires cells undergoing DNA synthesis to replicate.  Papillomavirus: stimulates cell growth and DNA synthesis.  Polyomavirus: stimulates cell growth and DNA synthesis.  Hepadnavirus: stimulates cell growth, cell makes RNA intermediate, encodes a reverse transcriptase.  Adenovirus: stimulates cellular DNA synthesis and encodes its own polymerase.  Herpesvirus: stimulates cell growth, encodes its own polymerase and enzymes to provide deoxyribonucleotides for DNA synthesis, establishes latent infection in host.  Poxvirus: encodes its own polymerases and enzymes to provide deoxyribonucleotides for DNA synthesis, replication machinery, and transcription machinery in the cytoplasm. PROPERTIES OF RNA VIRUSES  RNA is labile and transient.  Most RNA viruses replicate in the cytoplasm.  Cells cannot replicate RNA  RNA viruses must encode an RNA-dependent RNA polymerase.  The genome structure determines the mechanism of transcription and replication.  RNA viruses are prone to mutation.  The genome structure and polarity determine how viral mRNA is generated and proteins are processed.  RNA viruses, except for (+) RNA genome, must carry polymerases.  All (−) RNA viruses are enveloped. EXAMPLES  Picornaviruses, Hepeviruses, Astroviruses, Togaviruses, Flaviviruses, Caliciviruses, and Coronaviruses  (+) RNA genome resembles mRNA and is translated into a polyprotein, which is proteolyzed. A (−) RNA template is used for replication. For togaviruses, coronaviruses, and caliciviruses, early proteins are translated from the genome and late proteins from smaller mRNAs transcribed from the template.  Orthomyxoviruses, Paramyxoviruses, Rhabdoviruses, Filoviruses, and Bunyaviruses  (−) RNA genome is a template for individual mRNAs, but the full-length (+) RNA template is required for replication. Orthomyxoviruses replicate and transcribe in the nucleus, and each segment of the genome encodes one mRNA and is a template.  Reoviruses  (+/−) Segmented RNA genome is a template for mRNA (+RNA). (+) RNA may also be encapsidated to generate the (+/−) RNA and then more mRNA.  Retroviruses  (+) Retrovirus RNA genome is converted into DNA, which is integrated into the host chromatin and transcribed as a cellular gene. VIRAL GROWTH CURVES VIRAL DISEASE  Course of viral disease: invasion at portal of entry and primary infection; some viruses replicate locally, others enter the circulation and infect other tissues  Many viral infections have rapid course; lytic cycle  Some establish long-term persistent infections that last many years or a lifetime  2 types of persistent infections:  Chronic infections – virus detectable in tissue samples, multiplying at a slow rate; symptoms mild or absent  Latent infections – after a lytic cycle, virus enters a dormant phase; generally, not detectable; can reactivate and result in recurrent infections VIRAL DISEASE  Some persistent viruses are oncogenic  Oncogenic DNA viruses: Epstein–Barr virus (EBV), hepatitis B virus (HBV), human papillomavirus (HPV), human herpesvirus-8 (HHV-8), and Merkel cell polyomavirus (MCPyV)  Oncogenic RNA viruses: hepatitis C virus (HCV) and human T-cell lymphotropic virus-1 (HTLV-1).  Several viruses can cross the placenta causing developmental disturbances and permanent defects  TORCH/TORCHeS infections  Diagnosis of viral diseases:  Symptoms  Isolation in cell or animal culture  Serological tests for antibodies  Some tests for antigens  RT-PCR for genetic material VIRAL GENETICS  Mutations spontaneously and readily occur in viral genomes, creating new virus strains with properties different from the parental or wildtype virus  Mutations in essential genes can inactivate the virus (lethal mutations)  Mutations in other genes may produce antiviral drug resistance or alter the antigenicity or pathogenicity of the virus  Viral polymerases are error prone and generate many mutations during replication of the genome  RNA viruses lack a genetic error-checking mechanism  Rates of mutation for RNA viruses are usually greater than for DNA viruses  New virus strains can also arise by genetic interactions between viruses or between the virus and the cell (recombination)  Viruses with segmented genomes (e.g., influenza viruses and reoviruses) form hybrid strains on infection of one cell with more than one virus strain (reassortment) VIRAL VECTORS FOR THERAPY  Genetically manipulated viruses can be excellent delivery systems for foreign genes.  Viruses can:  Provide gene replacement therapy  Be used as vaccines to promote immunity to other agents or tumors  Act as targeted killers of tumors  Viruses that are being developed as vectors include retroviruses, adenoviruses, HSV, an adeno- associated virus (parvovirus), poxviruses (e.g., vaccinia and canarypox) and even some togaviruses QUESTIONS?