dna_viruses_part_1 9-16-24.pdf
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Microbiology and Host Defense DNA viruses: An Overview Dr. Lydia Bogomolnaya [email protected] DNA-containing viruses Objective: - To be able to describe major groups of clinically important DNA-containing viruses DNA-containing vi...
Microbiology and Host Defense DNA viruses: An Overview Dr. Lydia Bogomolnaya [email protected] DNA-containing viruses Objective: - To be able to describe major groups of clinically important DNA-containing viruses DNA-containing viruses DNA-containing viruses Clinically-relevant DNA viruses Virus Family Envelope Capsid DNA Clinically Important Clinical Symptoms Symmetry Structure Viruses Adenovirus No Icosahedral ds linear Adenovirus Pharyngitis, conjunctivitis, UTI Parvovirus No Icosahedral ss linear Parvo B19 virus Fifth disease in kids, anemia; RBC destruction in fetus Papillomavirus No Icosahedral ds circular Human Papilloma (HPV) Warts; can lead to cervical/anal squamous cell carcinoma Herpesvirus Yes Icosahedral ds linear Herpes simplex virus Oral lesions; cold sores; keratoconjunctivitis; genital herpes (HSV)-1 Herpes simplex virus Genital herpes (HSV)-2 Varicella-Zoster virus Chicken pox; zoster Epstein-Barr virus Mononucleosis Cytomegalovirus Cytomegalic inclusion disease (congenital abnormalities) HHV-6, HHV-7 Roseola HHV-8 Kaposi’s sarcoma Polyomavirus No Icosahedral ds circular JC virus Progressive miltifocal leukoencephalopathy BK virus Occurs in transplant patients, targets kidney Hepadnavirus Yes Icosahedral ds partial Hepatitis B virus Hepatitis B circular Poxvirus Yes Complex ds linear Smallpox Eradicated by live attenuated vaccine Molluscum contagiosum Umbilicated warts Monkeypox Similar to smallpox but less deadly DNA-containing viruses Adenoviruses Adenoviruses (from Latin adenos meaning gland) are medium-sized (70–90 nm), nonenveloped viruses exhibiting icosahedral symmetry, with fiber spikes protruding from capsomers that aid in host attachment. The genome is linear, double-stranded DNA, 26–48 kb in size. Replication occurs in the nucleus. Adenoviruses can cause acute respiratory diseases, conjunctivitis, and gastroenteritis. At least 67 types infect humans, especially in mucous membranes, and some types can persist in lymphoid tissue. Some of adenoviruses cause sarcomas in animals but no tumors in humans. Adenoviruses are valuable systems for molecular and biochemical studies of eukaryotic cell processes. They are also useful vectors for gene therapy approaches. DNA-containing viruses Parvoviruses Parvoviruses (from Latin parvus meaning small) are very small viruses with a particle size of about 18–26 nm. The particles have icosahedral symmetry, with 32 capsomeres, but they have no envelope. Virions are extremely resistant to inactivation. They are stable between a pH of 3 and 9 and withstand heating at 56°C for 60 minutes, but they can be inactivated by formalin, β-propiolactone, and oxidizing agents. The genome is linear, single-stranded DNA, averaging 5 kb in size. Replication occurs only in actively dividing cells; capsid assembly takes place in the nucleus of the infected cell. Human B19 virus targets erythroid progenitor cells. This virus causes hydrops fetalis (fatal anemia), aplastic anemia in sickle cell anemia patients, and erythema infectiosum (fifth disease, slapped cheeks syndrome)—an childhood disease characterized by an erythematous “slapped cheeks” rash. DNA-containing viruses Papillomaviruses Papillomaviruses are naked icosahedral viruses (55 nm in diameter) with double-stranded supercoiled DNA. The name refers to Latin papilla (nipple) and Greek –oma (tumor) and describes wart-like lesions produced by these viral infections. The human pathogen in the family is human papillomavirus (HPV). There are many types of human papillomaviruses, and certain high-risk types are causative agents of genital cancers in humans. Many animal species are infected by papillomaviruses, but those viruses are species-specific and do not infect humans. DNA-containing viruses Polyomaviruses Polyomaviruses are small (45 nm), nonenveloped, heat-stable, solubilization- resistant viruses. These viruses are structurally related to human papillomavirus. The name derives from Greek poly- (many) and –oma (tumor) and refers to the ability of some of these viruses to produce tumors in infected hosts. Polyomaviruses have cellular transforming ability in vitro but do not cause cancer in human. The most well-known human polyomaviruses are JC virus, the causative agent of progressive multifocal leukoencephalopathy and BK virus, associated with nephropathy in transplant recipients. DNA-containing viruses Herpesviruses Herpesviruses are family of large viruses 150–200 nm in diameter. The name refers to Latin herpes (creep), describing the spreading nature of skin lesions caused by these viruses. The nucleocapsid is 100 nm in diameter, with icosahedral symmetry and 162 capsomeres, surrounded by a lipid-containing envelope. The genome is linear, double-stranded DNA, 120–240 kb in size. Latent infections may last for the life span of the host, usually in ganglial or lymphoblastoid cells. Human herpesviruses include herpes simplex types 1 and 2 (oral and genital lesions), varicella-zoster virus (chickenpox and shingles), cytomegalovirus, Epstein-Barr virus (the cause of infectious mononucleosis), human herpesviruses 6 and 7 (T cell lymphotropic), and human herpesvirus 8 (associated with Kaposi sarcoma). DNA-containing viruses Hepadnaviruses Hepadnaviruses (from Latin hepa meaning liver) are small (40–48 nm), enveloped viruses containing circular, partially double-stranded DNA molecules that are about 3.2 kb in size. The DNA is a double-stranded circle that is unusual because the complete strand is not a covalently closed circle, and the other strand is missing approximately 25% of its length. Replication involves repair of the single-stranded gap in the DNA, transcription of RNA, and reverse transcription of the RNA to make genomic DNA. The virus consists of a 27-nm icosahedral nucleocapsid core within a closely adherent envelope that contains lipid and the viral surface antigen. The surface protein is characteristically overproduced during replication of the virus, which takes place in the liver, and is shed into the bloodstream. Hepadnaviruses such as Hepatitis B virus can cause acute and chronic hepatitis; persistent infections are associated with a high risk of developing liver cancer. DNA-containing viruses Poxviruses Poxviruses are the largest brick-shaped viruses 220–450 nm long × 140–260 nm wide × 140–260 nm thick. The particle structure is complex, with a lipid-containing envelope. The chemical composition of a poxvirus resembles that of a bacterium. Vaccinia virus is composed predominantly of protein (90%), lipid (5%), and DNA (3%). The name derives from Anglo-Saxon pokkes meaning pouch, referring to their characteristic vesicular skin lesions. Some are pathogenic for humans (smallpox, vaccinia, molluscum contagiosum); others that are pathogenic for animals can infect humans (cowpox, monkeypox) DNA-containing viruses Poxviruses The genome is linear, covalently closed, double-stranded DNA, 130–375 kb in size. Poxvirus particles contain about 100 proteins, including many with enzymatic activities, such as a DNA-dependent RNA polymerase. Replication occurs entirely within the cell cytoplasm. DNA-containing viruses Poxviruses Variola (Smallpox) virus Generally, two types of viruses are known: variola major and variola minor. The viruses are indistinguishable antigenically, their fatality rates differ considerably (>1% for variola minor, 3-40% for variola major). Smallpox virus is highly contagious (respiratory droplets, fomites) and can survive well in the extracellular environment. There is no known animal reservoir for variola virus. DNA-containing viruses Poxviruses Variola (Smallpox) virus In 1967, the World Health Organization (WHO) launched a program aimed at eradication of smallpox. WHO eradication campaign was based on two major reasons: (1) no extra-human reservoir of the virus was known to exist, and (2) asymptomatic carriage apparently did not occur. Global eradication of smallpox was confirmed in 1979 and accepted by WHO in 1980. Since then, the virus has been solely secured in two WHO-restricted laboratories: One at the United States Centers for Disease Control and Prevention (CDC) in Atlanta, Georgia, and the other at a similar facility in Russia. DNA-containing viruses Poxviruses Variola (Smallpox) virus Threat to bioterrorism: - smallpox is one of the most stable viruses; - it can remain stable for a long time, if freeze-dried; - it is unaffected by environmental conditions; - scab forms are stable for 1 year at room temperature and in one case, it was found stable for 13 years in a laboratory; - it has high infectivity among humans; - it is associated with high susceptibility among populations (routine vaccination against smallpox ended in 1972, and current vaccine supplies are limited); - there is a risk that healthcare providers may not promptly recognize and respond to early cases; - there is no specific antiviral treatment. Response plan and guidelines for such thread could be found on CDC website (https://www.cdc.gov/smallpox/) DNA-containing viruses Poxviruses Variola (Smallpox) virus Pathogenesis Smallpox virus enters through inhalation and replicates in the upper respiratory tract epithelium, spreads to the regional lymph nodes, infects phagocytic cells followed by development of viremia and dissemination to various organs such as liver, spleen, and skin. The incubation period is 12 to 14 days. Clinical manifestations are fever, chills, and malaise preceding lesions after 4 to 5 days. A dominant feature is a uniform papulovesicular rash that evolves to pustules over 1 to 2 weeks. Vesicles appear on face, arms, and lower extremities (all at the same time). DNA-containing viruses Poxviruses Variola (Smallpox) virus Pathogenesis Eosinophilic inclusions called Guarnieri bodies can be seen in the cytoplasm. Viral proteins interfere with host defenses causing depressed cell- mediated immunity. Enormous inflammatory responses were also accountable for main characteristics of illness. Death can result from the overwhelming primary viral infection or from bacterial superinfection. Vesicular scrapings and used for diagnosis. DNA-containing viruses Poxviruses Data as of August 6, 2024 In May 2022, multiple cases of mpox (formerly called monkeypox) were identified in several non-endemic countries. Mpox is spread through direct person-to-person contact, either via respiratory droplets or exposure to infectious lesions or other bodily fluids. It may also be passed from mother to child and may be contracted by touching contaminated surfaces or handling infected animals, animal feces or bedding. https://www.cdc.gov/poxvirus/monkeypox/response/2022/world-map.html Whether or not the virus can be sexually transmitted remains under investigation. DNA-containing viruses Poxviruses Similarities The symptoms of mpox and smallpox are very similar. Both viruses cause fever, chills, headaches, muscle aches and fatigue, as well as a characteristic rash with fluid-filled lesions that are concentrated on the face, mouth and extremities. DNA-containing viruses Poxviruses Differences The biggest differences between mpox and smallpox are that mpox has a much lower fatality rate and broader known host range than smallpox. Depending on the clade, mpox has a case fatality rate of 1-10%. Mpox vaccine JYNNEOS is a 2-dose vaccine developed to protect against mpox and smallpox infections. People need to get both doses of the vaccine for the best protection against mpox. Summary of Replication Cycles of Major Virus Families Presence Intracellular Location Multiplication Virus Family of Virion Replication of Formation of Virion Maturation Cycle (Hours) Envelope Genome Nucleocapsida DNA viruses Parvoviridae No Nucleus Nucleus Nucleus 24 Polyomaviridae No Nucleus Nucleus Nucleus 48 Adenoviridae No Nucleus Nucleus Nucleus 25 Hepadnaviridae Yes Nucleus Cytoplasm endoplasmic 12–24 reticulum membranes Herpesviridae Yes Nucleus Nucleus Membrane 15–72 Poxviridae Yes Cytoplasm Cytoplasm Cytoplasm 20 aThe synthesis of viral proteins always occurs in the cytoplasm.
