slides 2 viruses - 4.3

Vocabulary flashcards summarizing key pathogenic virus terms, their features, and related concepts for BIOL2700.

Virus

A non-cellular microbe consisting of nucleic acid enclosed in a protein capsid; some possess an envelope and spikes.

Herpes Virus family

HHV 1 & 2; VZV; EBV, and CMV

Hepatitis viruses

Hep A, B, and C

Pathogenic Viruses: Selected Types

• Herpes Virus family

• HHV 1 & 2; VZV; EBV, and CMV

• Hepatitis viruses

• Hep A, B, and C.

• Picornaviruses and common cold viruses

• Human Papilloma Virus (HPV)

• Measles

• Influenza

• HIV/AIDS, Zika, Ebola, Sin Nombre, SARS, JC, and D68 will get an update lecture during Unit 5

Pathogenic Viruses: Brief Review

• Non-cellular Microbes

• Consists of nucleic acid and capsid (protein)

• Some types possess envelope, spikes, accessory proteins

• Obligate intracellular parasites

• Nucleic acid enters host cell, directs operations

• New copies of viral nucleic acid, proteins made

  • Virus depends on host cell biochemical machinery

• Following assembly, new virions escape to infect new hosts

Obligate intracellular parasite

An organism (such as a virus) that can reproduce only inside a living host cell. - have to have a host - host allows them to multiply and spread

Pathogenic Viruses: Viral Attack

• Virus has ways of attacking

• Specific binding to host cell receptor

• Receptors involved in normal cell functions

• Virus may regulate cell division for its own replication

• Insertion of viral DNA into chromosome allows virus to hide from immune system

• Causes adjacent cells to fuse, allows cell to cell spread without leaving cell.

Pathogenic Viruses: Viral Attack - host defenses:

• Cell mediated immunity (T cells): infected cells killed.

• Antibodies intercept virions between cells, in fluids (best defense probs)

• Interferon produces anti-viral state, prevents replication (downregulation of transcription and translation)

Capsid

The protein coat that surrounds and protects a viral nucleic acid genome.

Envelope (viral)

A membrane derived from host cell lipid bilayer that surrounds some viruses; often contains viral spikes.

Spike protein

Viral surface glycoprotein that mediates attachment to host-cell receptors.

Latency (viral)

The ability of a virus to persist in a host cell without active replication, reactivating later to cause disease.

Interferon

Host cytokine that induces an antiviral state in neighboring cells, inhibiting viral replication.

Cell-mediated immunity

Immune defense driven chiefly by cytotoxic T cells that destroy virus-infected cells.

Pathogenic Viruses: Herpes Virus Family

• Human herpes viruses (HHV) now numbered

• But common names easier to use.

• As a family:

• ability to become latent;

• predilection for either nervous tissue or lymphocytes;

• ability to cause cancer. (#8 below)

• Of the more than 100 known herpes viruses, 9 routinely infect only humans.

Herpes roster:

• Herpes simplex (1-2), Varicella zoster (3), Epstein Barr (4), Cytomegalovirus (5), Roseoloviruses (6A, 6B, 7), Kaposi's sarcoma-associated herpesvirus (8).

Pathogenic Viruses: Herpes Simplex Viruses - HHV1

(above the waist)

• Typically oral, cold sores; flu-like symptoms, etc.

Pathogenic Viruses: Herpes Simplex Viruses - HHV2

(genital), STI and neonatal

• Painful, contagious sores on genitals, overlap w/ HHV1.

Pathogenic Viruses: Herpes Simplex Viruses

• HHV1 (above the waist)

• Typically oral, cold sores; flu-like symptoms, etc.

• HHV2 (genital), STI and neonatal

• Painful, contagious sores on genitals, overlap w/ HHV1.

• Latency

• Viruses enter nearby nerve cells, remain until activated by stress of some sort, cause disease, then return.

• Spread and treatment:

• Person to person by direct contact; spread within host by forming syncytia (fusion of cells), escape immune system.

• Virus may be secreted in saliva for up to 7 weeks after recovery and from genital lesions for 7-12 days

• Acyclovir helps; no cure, lifetime infection.

Pathogenic Viruses: Herpes family: Varicella Zoster

Varicella: chicken pox; Zoster shingles (HHV 3):

• Chickenpox (not a pox virus), respiratory, disease becomes systemic with fever, malaise, skin lesions.

• Very contagious; usually mild, esp. in children

• Virus can become latent in nerves (DRG of spinal nerves) like Herpes simplex

• Recurrence: shingles; rash, pain, covers dermatomal pattern

• Acyclovir can lessen symptoms

• Beware of salicylates + viruses (and fevers!): Reyes syndrome

• Vaccination: available for both Varicella & Zoster

Herpesviridae

Large enveloped dsDNA virus family able to establish lifelong latent infections; nine species infect humans.

Herpes Simplex Virus 1 (HSV-1 / HHV-1)

Herpesvirus causing orolabial lesions (“cold sores”); typically acquired above the waist.

Herpes Simplex Virus 2 (HSV-2 / HHV-2)

Herpesvirus commonly responsible for genital herpes and neonatal infections.

Syncytium

A multinucleated cell formed when viruses fuse adjacent host cells, allowing cell-to-cell spread.

Acyclovir

Antiviral drug that inhibits herpesvirus DNA polymerase, reducing symptom severity but not curing infection.

Varicella-Zoster Virus (VZV / HHV-3)

Herpesvirus that causes chickenpox (varicella) and, upon reactivation, shingles (zoster).

Shingles

Painful dermatomal rash due to reactivated VZV latent in dorsal root ganglia.

Reye’s syndrome

Potentially fatal encephalopathy and liver failure linked to salicylate use during viral illnesses such as varicella.

Pathogenic Viruses: Herpes family: EBV

• Epstein-Barr Virus (HHV 4)

• Cause of infectious mononucleosis

• Infects B cells and salivary glands

• Spread by respiratory droplets, kissing

• Sore throat, swollen glands and spleen

• Long lasting fatigue

• Lympho-civil war: cytotoxic T cellsattack infected, altered B cells.

• Same virus causes B cell cancer (Burkitt’s lymphoma) in Africa

• The occurrence of cancer also has some relationship to malaria exposure

Epstein–Barr Virus (EBV / HHV-4)

Herpesvirus transmitted via saliva; causes infectious mononucleosis and is linked to Burkitt’s lymphoma.

Infectious mononucleosis

EBV-mediated illness marked by sore throat, lymphadenopathy, splenomegaly, and fatigue.

Burkitt’s lymphoma

Aggressive B-cell cancer in Africa associated with EBV and malaria exposure.

Cytomegalovirus (CMV / HHV-5)

Herpesvirus producing enlarged host cells; usually asymptomatic but dangerous to fetus and immunosuppressed patients.

Pathogenic Viruses: Herpes family: Cytomegalovirus

• CMV (HHV5): Infection results in enlarged cells (hence, “Cytomegalo-”) - not the most scary herpes

• Widespread asymptomatic infections, latency

• Virus shed in body fluids: sex, birth, transplants

• Problem for unborn, immunosuppressed, transplant patients; major cause of viral- induced birth defects.

Pathogenic Viruses: Herpes family: Roseoloviruses

Cause of Sixth disease (roseola infantum, exanthem subitum)

• Classic presentation of a fever of rapid onset followed by a rash, both lasting 3-5 days. Complications may include febrile seizures, with serious complications being rare.

• Spread is usually through the saliva of those who are otherwise healthy. However, it may also spread transplacentaly during pregnancy.

Roseolovirus (HHV-6 & HHV-7)

Herpesviruses that cause roseola infantum (sixth disease) featuring high fever followed by rash.

Kaposi’s sarcoma–associated herpesvirus (KSHV / HHV-8)

Herpesvirus transmitted mainly by saliva; causes vascular cancer Kaposi’s sarcoma, common in AIDS.

Pathogenic Viruses: Herpes family: Kaposi's sarcoma-associated herpesvirus

HHV-8

• Causes Kaposi's sarcoma, a cancer commonly occurring in AIDS patients.

• The sarcoma is a cancer that develops from the cells that line lymph or blood vessels.

• KSHV is transmitted mainly through saliva, but also transmissible via organ transplantation

Pathogenic Viruses: What is Hepatitis?

inflammation of the liver

• Liver especially important in metabolism

• Breakdown of drugs, toxins, waste products

• Damage results in accumulation of bilirubin

• Bilirubin is a stage in hemoglobin breakdown

• Results in yellow color: jaundice

• Hepatitis can be caused by several different viruses

• Hepatitis A, B, and C viruses all cause liver damage, but are unrelated viruses.

Hepatitis

Inflammation of the liver leading to jaundice from bilirubin buildup.

Bilirubin

Yellow hemoglobin breakdown product that accumulates during liver dysfunction, causing jaundice.

Hepatitis B Virus (HBV)

Enveloped partially dsDNA hepadnavirus spread by blood, sex, or birth; chronic infection raises liver-cancer risk.

Pathogenic Viruses: Hepatitis B

• A DNA virus: “Hepadnavirus”

• Hepatitis B released from live cells, so

accumulates in high numbers in body fluids.

• Blood of infected person is rather infectious

• Cuts, piercing, sex, childbirth, etc.

• Large amounts of empty capsids ties up

antibodies.

• After exposure, long incubation, long disease

• 10% have chronic infections

• The younger the host, the likelier chronic

infection

• Chronic infection correlated with liver

destruction

• Liver tissue replaced by scar tissue; liver

failure

• Long term exposure to virus increases risk

of liver cancer

• Insertion of HBV DNA into

chromosome may activate oncogenes

• Vaccination: routine for children starting ~1991

• Recombinant vaccine.

Pathogenic Viruses: Hepatitis A

A small RNA virus, “Picornavirus” (little)

• Transmitted by fecal-oral route

• Incubation for 1 month, followed by fever, nausea, anorexia, jaundice

• T cells attack infected liver cells

• No chronic infections, patients recover.

Note comparisons to Hepatitis B:

• RNA vs DNA

• Shorter disease, few long term problems

• Mode of spread completely different

Pathogenic Viruses: Hepatitis C

• Another RNA virus, different group: “Flavivirus”

• Causes chronic infections >80%

• Often mild with few symptoms until damage

• Long period between infection and damage

• Long term infections increase risk of cancer.

• Transmission like Hep B: blood, sex, transplants

• Curable with sofosbuvir/ledipasvir: blocks viral proteins

HBV empty capsids

Non-infectious particles produced by HBV that bind antibodies, helping the virus evade immunity.

Hepatitis A Virus (HAV)

Non-enveloped RNA picornavirus transmitted fecal-orally; causes acute self-limited hepatitis without chronicity.

Hepatitis C Virus (HCV)

Enveloped RNA flavivirus spread via blood and sex; leads to chronic hepatitis in >80% of cases and is curable with sofosbuvir/ledipasvir.

Sofosbuvir/Ledipasvir

Direct-acting antiviral combination that blocks HCV proteins, achieving high cure rates.

Human Papillomavirus (HPV)

Non-enveloped dsDNA virus with many serotypes causing warts and cervical or other anogenital cancers.

Pathogenic Viruses: Human Papilloma Virus (HPV)

Many Serotypes:

•1,2-plantar and common warts

• 6,11-condylomata and laryngeal warts

• 16,18, 31 and others- anogenital malignancies

Pathogenic Viruses: HPV

Genital Warts

•Usually caused by HPV 6 or 11

• Prevalence had increased 2-10x during 30 year period prior to vaccine;

Now down ~56%

• Most often found on penile shaft and anus in men, vulva in women

•Spontaneous regression seen in 20% of cases

•Treatments are ablative in nature

Respiratory

•Also caused by 6 and 11

• Pre-school children-bronchiolitis

•Adults-orogenital contact

•Potentially increasing in HIV+ individuals

Anogenital Malignancy

•Caused by high risk HPVs-16, 18, 31 and others

•Occurs mainly in older women-average age 54 years

•Over 35% mortality

•Associated with increased number of sexual partners

•Prophylactic and Therapeutic Vaccines are available

Genital warts - hpv

Lesions usually produced by HPV types 6 and 11 on external genitalia.

•Usually caused by HPV 6 or 11

• Prevalence had increased 2-10x during 30 year period prior to vaccine;

Now down ~56%

• Most often found on penile shaft and anus in men, vulva in women

•Spontaneous regression seen in 20% of cases

•Treatments are ablative in nature

respiratory - hpv

•Also caused by 6 and 11

• Pre-school children-bronchiolitis

•Adults-orogenital contact

•Potentially increasing in HIV+ individuals

Anogenital malignancy - hpv

Cancers of cervix, anus, oropharynx linked to high-risk HPV types 16, 18, 31, etc.

•Caused by high risk HPVs-16, 18, 31 and others

•Occurs mainly in older women-average age 54 years

•Over 35% mortality

•Associated with increased number of sexual partners

•Prophylactic and Therapeutic Vaccines are available

Picornaviruses - pico, very small viruses

Very small non-enveloped RNA viruses including enteroviruses, rhinoviruses, and HAV.

• Small RNA viruses (“pico” = very small)

• About 25 nm, near the size of a ribosome

• Many kinds of troublemakers, but two basic themes…

• Enteric viruses

• includes the previously mentioned Hepatitis A, as well as polio

• Only some cases of polio resultin paralysis

• Includes Enterovirus A-D

• Cause of many cases of“stomach flu”

• D68 can cause a “polio-like” syndrome

• Rhinoviruses: major cause of common cold

• Rhino refers to the nose

Enterovirus - picornavirus

Group of picornaviruses infecting GI tract; includes poliovirus, Coxsackie, echoviruses, and D68.

• includes the previously mentioned

Hepatitis A, as well as polio

• Only some cases of polio result in paralysis

• Includes Enterovirus A-D

• Cause of many cases of “stomach flu”

• D68 can cause a “polio-like” syndrome

picornaviruses - rhinoviruses

major cause of common cold

• Rhino refers to the nose have many serotypes

• Variants, caused by easy mutation of RNA

• Immune system can’t recognize all differences, but some protection with age.

• Multiplies in narrow temperature range, nose/sinus cooler than body temperature

Rhinoviruses & The Common Cold - Other cold viruses (not Picornaviruses)

• Coronavirus (As you know, some versions can cause SARS. Full Report Coming in Unit 5!)

• Adenovirus (DNA virus), some serotypes cause GI infections

Poliovirus

Enterovirus that can invade motor neurons, causing paralytic poliomyelitis in a subset of infections.

Coxsackievirus

Enterovirus associated with herpangina, hand-foot-mouth disease, myocarditis, and meningitis.

Hand, Foot & Mouth Disease

Pediatric illness featuring oral ulcers and vesicular rash on hands/feet, caused by Coxsackie A viruses.

Enterovirus D68

Picornavirus capable of respiratory disease and rare polio-like acute flaccid myelitis.

Rhinovirus

Picornavirus with >100 serotypes; principal cause of the common cold, thriving at cooler nasal temperatures.

Morbillivirus (Measles virus) - Morbillivirus: non-segmented., linear., ssRNA, helical capsid,

enveloped

Enveloped ssRNA virus transmitted by airborne droplets; extremely contagious.

• First described in 7th century

• Measles transmission is primarily person to person via large respiratory droplets. Airborne transmission via aerosolized droplet has been documented in closed areas (e.g., office examination room) for up to 2 hours after a person with measles occupied the area.

• Measles is highly communicable, with >90% among susceptible persons. Measles may be transmitted from 4 days prior to 4 days after rash onset. Maximum communicability occurs from onset of symptoms through the first 3-4 days of rash.

• Measles is a human disease. There is no known animal reservoir, and an asymptomatic carrier state has not been documented.

Measles - virulence

• Portal of entry:

– Respiratory mucus membrane.

• Attachment:

– Hemagglutinin: like influenza uses

• Evade the immune system:

– Immunosuppression:

• The measles virus blocks TH proliferation response to IL-2.

• The virus also destroys memory B-cells!

• Measles virus infection diminishes preexisting antibodies that offer protection

from other pathogens. Mina. Et al. Science 01 Nov 2019:Vol. 366, Issue 6465

• Destruction of tissue:

The maculopapular rash is caused by immune T-cells targeted to the infected endothelial cells of the small blood vessels.

measles - maculopapular

describes a rash that contains both macules and papules. A macule is a flat discolored area of the skin, and a papule is a small raised bump. A maculopapular rash is usually a large area that is red, and has small, confluent bumps.

measles - signs & symptoms

• Fever - can kill people

• Malaise

• Maculopapular rash on palms and

soles

• sore throat

• Rhinorrhea

• Cough

• Conjunctivitis

• Koplik spots: Found in the mouth, these spots look like tiny grains of white sand, each surrounded by a red ring.***

measles - Quick Summary

• Reservoir: Human

• Transmission: Respiratory/Airborne

• Temporal pattern: Peak in late winter–spring

• Communicability:4 days before to 4 days after rash onset

measles vaccine -

Measles vaccine is a live, attenuated

measles virus grown in chick embryo

tissue culture. In the United States, it

is given as part of the MMR vaccine.

• Vaccine is about 95% effective

• Cases continue to occur among

those who do not develop or

retain good immunity, or those

who avoid vaccinations.

Koplik spots

Tiny bluish-white oral lesions pathognomonic for measles infection.

Subacute sclerosing panencephalitis (SSPE)

Rare, fatal, late measles complication with progressive brain degeneration years after infection.

MMR vaccine

Live attenuated measles-mumps-rubella vaccine providing ~95 % protection against measles.

Orthomyxovirus

Enveloped RNA viruses with segmented genomes; includes influenza A, B, and C. - causes Influenza: a wide-spread and still very dangerous

respiratory disease

• Types A,B,C

• Virus has a segmented genome

• 8 different RNA molecules

• Spikes: Hemagglutinin and Neuraminidase

• Major antigens recognized by immune system

Antigenic drift and shift

Drift: small mutations, making host susceptible

• Requires new vaccine each year

• HA and NA accumulate mutations

• immune response no longer protects fully

• sporadic outbreaks, limited epidemics

Shift: major mixing of RNAs, whole new virus

• “new” HA or NA proteins

• pre-existing antibodies do not protect

• may get pandemics

Hemagglutinin (HA)

Influenza spike mediating viral attachment to respiratory epithelial cells.

Neuraminidase (NA)

Influenza spike enzyme that cleaves sialic acid, allowing progeny virions to exit cells.

Antigenic drift

Gradual accumulation of point mutations in HA/NA that cause seasonal influenza epidemics.

Antigenic shift

Abrupt genetic reassortment of influenza segments generating novel HA or NA, leading to pandemics.

Pathogenic Viruses: “Flu”?

• True influenza

– influenza virus A or influenza virus B (influenza virus C infections are much milder)

• Febrile respiratory disease with systemic symptoms caused by a variety of other organisms often called “flu”

Nature of Influenza

Attack on respiratory tract

• Kills ciliated epithelial cells, allows bacterial infections.

• Release of interferon causes symptoms

H antigen (hemagglutinin) for attachment!! - get into host!!

• The fact that it agglutinates RBCs is an artifact

N antigen: neuraminidase

• Cuts off the sugar on the glycoprotein receptor

• Allows new virions to escape from cell without getting stuck - escape the host!!

Influenza A virus

Orthomyxovirus subtype capable of infecting humans, birds, pigs; subject to drift and shift.

Influenza vaccine

Annual inactivated or live attenuated formulation based on predicted circulating strains of HA/NA.

Pathogenic Viruses: Influenza - history

• Changes in H and N (antigenic shift)

– Mixing of viruses that infect birds, pigs, produce new strains able to jump to humans.

– New antigenic type leaves population unprotected

– Numerous epidemics throughout history

• Flu of 1918-1919 killed 20 million

– Asia watched very carefully: bird flu?

• Flu vaccines made from deactivatedviruses

– Slow process (vaccine made in eggs), so every year correct strains are “guessed”

.

– Cell culture would be quicker but more $

flu meds

•Rimantadine: Type A only, needs to be given early

•Amantadine: Type A only, needs to be given early

•Zanamivir: Types A and B, needs to be given early

•Oseltamivir: Types A and A, needs to be given early

flu spread via..

Aerosol

• 100,000 TO 1,000,000 VIRIONS PER DROPLET

• 18-72 HR INCUBATION

flu body response

Lots of Interferon!- Side Effects: Fever, myalgia, fatigue, malaise, cell-mediated immune response

Antibody Induction! IgG and IgA

• IgG less efficient but lasts longer

• antibodies to both HA and NA important

• antibody to HA more important (neutralize virus)

major causes of influenza virus - associated death

•Bacterial pneumonia

•Cardiac failure

•90% of deaths in those over 65 years of age

flu diagnosis

Isolation

•Nose or Throat Swab

•Tissue or Egg Culture

•Serology (Blood Analysis)

•Provisional: Clinical picture + Outbreak

flu complications

• Secondary bacterial infection

• Strept pneumoniae

• Staph aureus

• Hemophilus influenzae

• Myositis (rare, > in children,

> with type B)

• Cardiac complications

• Liver and CNS

• Reye syndrome

• Peripheral nervous system

  • Guillian-Barré syndrome

Reye syndrome

Acute encephalopathy and hepatic dysfunction linked to aspirin use during viral infections like flu or varicella.

Guillain-Barré syndrome

Autoimmune demyelinating neuropathy that can rarely follow influenza infection or vaccination.- occurs after the virus, own immune system attacks the myelin