Viruses Flashcards
What do viruses need?
Most have an envelope, a core = capsid, and RNA or DNA
Viral RNA-dependent RNA polymerase required for (–) reading frame
Retrovirus RNA is transcribed in a retrograde fashion requiring a viral reverse transcriptase (RNA-dependent DNA polymerase)
Retro virus characteristics
Diploid
nuclear reproduction: reverse transcriptase
What viruses use V RNA-dependent RNA polymerase?
Orthomyxo, Paramyxo, Filo, Bunya, Arena, Rhabdo.
Rhabdo is bullet-shaped. (rabies, e.g.)
Special stuff about Reo
+/- RNA, double stranded, not enveloped
Special stuff about pox
replicates in cytoplasm, DNA-dependent RNA polymerase, enveloped
Parvo virus
uses DNA, single strands, not enveloped
Major digestive viruses
Rotavirus- childhood gastroenteritis, vaccine preventable, number 1 worldwide
Norovirus (Norwalk), Gastroenteritis, number one in the US
Orthomyxovirus
= Influenza
Envelope with surface glycoproteins hemagglutinin (H) and neuraminidase (N)
Neuraminidase inhibitors
Type A can come from animals and can become pandemic. Types B and C not so bad.
antigenic drift–> small changes, epidemics
antigenic shifts –> big changes, pandemics
CHILD + FLU (or chickenpox) + ASPIRIN → REYE SYNDROME
Yearly inactivated vaccines
Paramyxoviruses
- ssRNA with envelope:
- Parainfluenza
- Mumps
- Measles
- Respiratory syncytial virus
- Human metapneumovirus (common cold)
Produce multinucleated giant cells (SYNCYTIA) via a cell fusing factor
Parainfluenza
a Paramyxovirus
Most common cause of croup laryngotracheobronchitis (barking cough, steeple sign)
Respiratory Syncytial Virus Rx
Paramyxovirus
major cause of bronchiolitis and pneumonia in infants
RX- Palivizumab against F-protein
Mumps Virus
Paramyxovirus
Enters from salivary secretions (intimate contact) via the pharynx or conjunctiva
Painful enlargement of the salivary glands
Epididymoorchitis in males, which can cause sterility
Prevention: - Immunize with MMR live vaccine
Measles Virus (Rubeola)
Paramyxovirus
Koplik spots of mouth precede T-cell mediated rash
Inclusion body encephalitis and/or with chronic infection
subacute sclerosing panencephalitis (SSPE)
93.3% vaccinated = herd immunity
DX- multinucleated measles giant cells (Warthin-Finkeldey cells)
Prevention: MMR live vaccine. Vaccination rate in CO: 86%
Hepatitis Viruses
Hep A: PicoRNAviridae (Fecal-Oral transmission). Mostly mild, jaundice.
Hep B: HepaDNAviridae. Dane particle- oncogenic transforming virus
parenteral/ sex transmission
enveloped
–> hepatocellular carcinoma
Hep C: Flaviviradae. Hepatocellular carcinoma
parenteral/ sex transmission
enveloped
–> hepatocellular carcinoma
Hep D: Unassigned virion. (delta antigen)
parenteral/ sex transmission
Onset: Abrupt w/ superinfection or hepatitis B
co-infection
enveloped (by Hep B)
Hep E: Enteric. HepEviridae, fecal-oral transmission
Prevention of various hepatitis viruses
Hep A vaccine
Hep B vaccine
Hepatitis - Viral Serology (know this down cold)
Acute B - HBsAg: Acute B, &D coinfection
HBcAb- Acute B
Anti-HDV- B& D Co-infection
Acute A- Anti-HAV IgM
Prior C- Anti-HCV
Acute C- Anti HCV
Chronic C- Anti Hcv
Hep E- Anti- HEV HEV RNA
HBsAb IgG with nothing else means they’ve been vaccinated against B.
Retroviruses
use reverse transcriptase
Oncornaviruses: HTLV 1 , HTLV 2
HTLV-I –> T cell leukemia/ lymphomas, myelopathy
Lentiviruses are also retroviruses: HIV 1, HIV 2
Lentiviruses
are retroviruses
- can cause multinucleated cells (cell to cell fusion of macrophages)
HIV 1, HIV 2
Can cause AIDS dementia, wasting syndrome
Attach to CD4 receptor & CCR5 (macrophage) or CXCR4 (TH cell) coreceptors
Western Blot (tests for antibodies against viral proteins),
Rx – Antiretrovirals
Important HIV genes
gag (early marker of infection from capsid)
pol (reverse transcriptase, integrase. Allows DNA integration into host)
env (binds CD4&CCR5 (macrophage) or CXCR$ (Th cell)
LTR
Herpes viruses
produce intranuclear inclusions and multinucleated giant cells
capable of latency
1 & 2 are neurotropic
CMV and EBV are lymphotropic
Types:
HHV 1- herpes simplex 1 HHV 2- herpes simplex 2 HHV 3- varicella zoster virus HHV 4- Epstein Barr virus (oncogenic transforming virus) HHV 5- Cytomegalovirus (oncogenic)
6th and 7th apparently cause 6th disease (rash)
HHV 8- Kaposi Sarcoma-associated herpesvirus (oncogenic)
Herpes Simplex
Have intranuclear acidophilic Cowdry type A (eosinophilic) inclusions w/ margination of the nuclear chromatin
1- cold sores, gingivostomatitis (–>oropharyngeal blister in kids), fatal sporadic encephalitis
2- genital region. Whitlows- erythematous lesions on toes or nail cuticle.
Rx- acyclovir
Varicella-Zoster
Chickenpox (varicella)
Usually transmitted by saliva
Rash: head & trunk –> extremities. asynchronous and centripetal spread)
Shingles (zoster)
Older individuals with reactivation of latent infection
Skin areas innervated by sensory nerves of the dorsal root ganglia
Trigeminal nerve is common distribution
prevention: 2 doses of varicella (VAR) (kids)
Zoster vaccine for older people
Epstein-Barr Virus
Attach via CD21
= Complement receptor 2 = EBV receptor
Infectious mononucleosis
Atypical activated T-lymphocytes (Downey cells)
Hodgkin lymphoma, Burkitt lymphoma, central nervous system lymphomas, & nasopharyngeal carcinoma
dx- heterophile antibodies (monospot)
Cytomegalovirus
Owl-eye basophilic intranuclear inclusions
Transmission:
Transplacental - primary infection pregnant mother
Neonatal - cervical or vaginal secretions during birth
Perinatal -breast milk from a mother who has active infection
Saliva – common during preschool years
CMV mononucleosis-syndrome with fever, fatigue and atypical lymphocytes
Congenital cytomegalovirus infection (cytomegalic inclusion disease of the newborn)-in utero infections with jaundice, purpura, hepatosplenomegaly and central nervous system development disorders
Poxviridae
Replicate in the cytoplasm of host cell
Smallpox
Molluscum contagiosum
- Common self-limited viral disease caused by Poxvirus
look for cytoplasmic inclusions
Papillomaviridae (p.k.a. Papovariedae)Human Papilloma Virus
Oncogenic transforming viruses:
Viral E6 inhibits p53 protein and E7 inhibits pRB protein
High-risk - types 16 and 18 responsible for most cancers and high grade dysplasias
prevention: vaccination (females) and physical barriers
Polyomaviridae (p.k.a. Papovariedae)BK and JC Viruses
BK - Renal disease (failure) in AIDS or post-transplant patients
Dx - BKV DNA by PCR or urine cytology with decoy cells (basophilic nuclear inclusions)
JC - Progressive multifocal leukoencephalopathy in AIDS or post-transplant
Dx - JCV DNA by PCR
Adenoviridae
Acute respiratory disease – serotypes 4,7 &21) upper respiratory infections in kids/young adults that can progress to pneumonia
Gastroenteritis - adenoviruses that lead to diarrhea
Pharyngoconjunctivitis – pink eye and sore throat
Prevention – live adenovirus vaccine
Parvoviridae
Parvovirus B19
Naked ssDNA in segments (some positive, others negative)
Erythema infectiosum (fifth disease)
Fever, arthralgias and cheek rash children
Aplastic anemia (infects erythroblasts)
Can cause hydrops fetalis via in utero infection
Viral Encephalitis
Western/ Eastern Equine Encephalitis (alpha virus)
Lt. Louis encephalitis virus (flavivirus) –> St Louis encephalitis
West Nile virus (flavivirus)
Dengue virus (flavivirus)
Colorado tick fever virus (reovirus) –> headaches behind the eyes, photophobia, rash
La Cross virus (bunyavirus)
Other viruses that can cause encephalitis: HSV, VZV, Influenza, Enteroviruses, Rabies, Mumps, Measles
Arboviruses
Arthropod borne viruses
Togaviridae: WEE, EEE, VEE encephalitis, chikungunya & rubella
Flaviviradae
Yellow and dengue fevers, St. Louis and Japanese encephalitis, West Nile virus, hepatitis C
Bunyaviradae
California encephalitis, Rift Valley fever, hantavirus
Togaviruses
Alphaviruses
Chikungunya: get viremia with acute febrile illness with malaise, rash and arthritis
Eastern and western equine encephalitis (EEE, WEE)
Rubivirus (no arthropod vector) – rubella (German measles) Congenital rubella (TORCH syndrome)
Flaviviruses (more to follow)
Yellow fever virus, Dengue virus, St. Louis encephalitis, Japanese encephalitis, West Nile virus, hepatitis C virus
Bunyaviruses
California encephalitis, Rift Valley fever, pappataci (sandfly) fever, hantavirus pulmonary syndrome (more in emerging pathogens slides)
Rubella/Rubivirus
= German measles
Congenital rubella syndrome affects the eyes, heart and brain
Infection occurred during 1st trimester of pregnancy
Flaviridae
Flaviviruses
Mosquitoes
St. Louis encephalitis (SLE): viremia (usually asymptomatic), in some CNS involvement causes encephalitis inflammation and neuronal degeneration
West Nile encephalitis (WNE): viremia (usually asymptomatic), mild, flu-like cases (“West Nile fever“), more severe “West Nile encephalitis” or “West Nile meningitis” which can lead to death
Yellow fever: viremia with severe systemic disease (fever, headache, nausea and vomiting) followed by liver damage and intestinal hemorrhages (jaundice, shock and death)
Dengue fever: virus replicates in the skin and then goes to lymphoid tissue followed by a viremia which results in fever and rash lasting 3-9 days (self-limited) but can get dengue hemorrhagic fever (immunopathologic processes produce extreme vascular permeability, shock and death and associated with serotype 2)
Picornaviruses
Heparnavirus – discussed with hepatitis viruses
Rhinoviruses - Attach via ICAM-1 receptor to respiratory epithelial cells
Enteroviruses (Poliovirus, Coxsackievirus, Echovirus, etc.)
- spread fecal-oral
Enteroviruses
Polioviruses
Prevention- Inactive (Salk vaccine), oral (Sabin vaccine)
Coxsackie A & B can cause aseptic meningitis. A
Group A - herpangina, acute hemorrhagic conjunctivitis & hand-foot-and-mouth disease
Group B - pleurodynia, myocarditis, pericarditis, and hepatitis
Echoviruses
Rhabdoviridae/Rabies
bullet-shaped (think: shoot the rabid dog)
(encephalitis) via acetylcholine receptor with retrograde axoplasmic transport to dorsal root ganglia and spinal cord
Negri bodies (Neurons accumulate ribonucleoprotein as intracytoplasmic inclusions)
hydrophobia, anxiety, dilation of pupils
Once symptomatic death is almost certain despite optimal supportive care
Prevention: vaccines for dogs and cats
Emerging Infections
cholera, cryptosporidiosis, Ebola hemorrhagic fever, dengue fever, hantavirus pulmonary syndrome, hep C, HIV/ AIDS, influenza, legionnaires’ disease and Pontiac fever, malaria, MRSA, SARS, VISA/ VRSA, Staph aureus, West Nile virus
Of Biodefense importance: Ehrlichiosis, Hep C and E, among many others.
Enterovirus 68
not polio, but polio-like
acute flaccid myelitis, new outbreak in US 2014-2015
Appears to be related to enterovirus 68
Zika Virus
Appears to be associated with development of Guillain-Barré syndrome
Appears to be associated with microcephaly, lissencephaly and other neurologic malformations with in utero infections (highest risk in second trimester)
Vector is aedes mosquito species
Viral Hemorrhagic Fevers
RNA viruses
Arenaviridae – South American hemorrhagic fever viruses and Lassa Fever
Filoviridae – Ebola (4 subtypes) and Marburg viruses
Bunyaviridae – Rift Valley fever & Crimean-Congo hemorrhagic fever
Flaviviridae – Dengue hemorrhagic fever
Rhabdoviridae – Bas-Congo virus hemorrhagic fever
usually insect vector
Ebola (hemorrhagic fever)
Person-to-person transmission via blood or body fluids (urine, saliva, sweat, feces, vomit, breast milk, and semen)
Symptoms appear 2 to 21 days after exposure
25-90% mortality
Dengue Fever
Classic dengue fever, “break bone fever,” - acute onset of high fever 3–14 days after the bite, frontal headache, retro-orbital pain, myalgias, arthralgias, hemorrhagic manifestations, rash, and low white blood cell count
Dengue hemorrhagic fever - Fever lasting 2–7 days with any hemorrhagic manifestation, thrombocytopenia, evidence of increased vascular permeability. Can have severe abdominal pain, CNS symptoms, shock.
RX- supportive, IV fluids, Dextran 40
Powassan virus
Tick (Ixodes) borne virus found mostly in Canada, northeast and Great Lakes regions, and Russia
1 week to 1 month incubation and infections range from asymptomatic to encephalitis and meningitis
Fever, headache, vomiting, weakness, confusion, loss of coordination, speech difficulties, and seizures
50% develop permanent neurologic deficits
10% die
West Nile Virus
Vector - mosquito (lots of different species)
Human to human via blood or milk
Acute viremia
Usually subclinical infections or viral syndrome (20%)
Maculopapular rash in 50% with viral syndrome
Meningoencephalitis (
Chikungunya Virus
Symptoms begin 3–7 days after being bitten by infected
Aedes mosquitos
Most common symptoms are fever and joint pain Self limited (1 wk. most symptoms and months for joints)
SARS Virus
Severe acute atypical respiratory syndrome due to a novel coronavirus
No cases since 2003 outbreak
MERS Coronavirus
Middle East Respiratory Syndrome Coronavirus
Asymptomatic to severe acute respiratory syndrome (fever and pneumonia) in person coming from Arabian peninsula or in close contact with MERS patient
Spread via saliva, respiratory droplets
Bunyaviridae
California encephalitis- California encephalitis virus via mosquitos in Kern and Marin counties, CA
La Crosse encephalitis- La Crosse virus via mosquitos in Eastern U.S.
Hantavirus – worldwide
Hemorrhagic fever with renal failure – Asia and Europe
Pulmonary syndrome - spread via aerosolized rodent excrement causing pulmonary edema with 40% mortality; in U.S. around “four corners” region (Arizona, Colorado, New Mexico and Utah)
Deer mice is carrier in Four Corners region
serology to “Sin Nombre” virus; p.k.a “Four Corners virus”
Elizabethkingia spp.
Ubiquitous soil bacteria that also live in the gut of Anopheles gambiae mosquitos
Can colonize human respiratory tract
E. anopheles 2015-16 community acquired outbreak from unknown source in debilitated elderly around Milwaukee, Wisconsin has killed 15 (of 52 patients) as of March, 2016
Bioterrorism CDC Categories
Category A - can be easily disseminated or transmitted from person to person; result in high mortality - anthrax, smallpox (variola major), Viral hemorrhagic fevers (arenaviruses, bunyaviruses - hantaviruses, rift valley fever, crimean congo hemorrhagic fever, flaviruses- dengue, filoviruses- ebola & marburg)
Category B - moderately easy to disseminate; result in moderate morbidity rates and low mortality rates; - Brucellosis (brucella species), Ricin toxin, water safety threats (vibrio cholerae, e.g.)
Category C - emerging pathogens that could be engineered for mass dissemination. Emerging infectious diseases such as Nipah virus and hantavirus. SARS and MERS.
Anthrax and bioterrorism
Rx- 3 concurrent antimicrobials
Anthrasil (anthrax immune globulin intravenous [human]) for inhalational anthrax
vaccine: Ava/BioThrax (used for combatants)-
Smallpox in bioterrorism
Smallpox
Variola virus
Respiratory transmission
Dx –Characteristic deep skin lesions with centrifugal pattern (mostly face and extremities) and synchronous development on individual areas of the body
Smallpox vaccine – live vaccinia virus preparation
