HSS1101: Viruses

HSS1100

Basic components of viruses

• Nucelic acid: infectious genetic material

• Protective coat (capsid)

• Surface antigens: Protein or carb. Highly variable

Steps for virus replication

• Adsorption - Viruses adsorb to receptors on the cell surface.

• Penetration and uncoating - The virus enters the cell, the protein coat is lost and the nucleic acid released; it becomes undetectable (eclipse).

• Synthesis of nucleic acid and protein - The viral nucleic acid redirects the cell metabolism to produce viral protein and nucleic acid.

• Assembly-Maturation - Viral components are assembled to form mature (infective) virus particles.

• Release - Newly formed virus particles are released by either lysis (destruction) of the cell or budding through the cell membrane

Main approaches to viral diagnosis

A. Detection of viruses in clinical specimens.

B. Detection of the immune reactions triggered by the virus in the patient, i.e., detection of antibodies in the patient's blood.

• includes

  • cytopathic effect, hemagglutination, immunofluorescence

Detection of viruses in clinical specimens 

1. Visualization of electron microscopy (E.M.) 

2. Effect after inoculation into cell cultures: this requires multiplication, i.e., time 

3. Direct detection of viral antigens in clinical specimens themselves by immunological methods 

Visualization by electron microscopy

• method for dection of virus in clinical specimens 

• since viruses are invisible by light microscopy and very high magnification required.

• Only used for a few viruses which happen to be present in very large numbers in clinical specimens

Cytopathic effect

• visible modifications of infected cells caused by virus

• An effect after inoculation into cell cultures

hemagglutination

• An effect after inoculation into cell cultures 

• Some viruses agglutinate red blood cells added to the cell cultures 

Immunofluorescence

• An effect after inoculation into cell cultures 

• will reveal the presence of viral antigenic material within the infected cell culture, even if there is no visible damage caused by the multiplying virus

Detection of immune reactions triggered in the patient's immune system

• i.e. detection of antibodies in patient’s blood

Immunity tests

• presence or absence of antibody against a given virus

• a method for detection of immune rxns triggered in patient’s immune system 

Diagnostic tests

• a method for detection of immune rxns triggered in patient’s immune system 

• rise in antibody or high antibody titer against a given virus = evidence that this particular virus has recently caused a viral illness

Respiratory viruses

• A group of viruses which are found mainly in the respiratory tract and produce respiratory tract disease. They belong to different virus families

• Includes: 

  • influenza viruses

  • parainfluenza viruses

  • respiratory syncytial viruses

  • rhinoviruses

  • coronaviruses

Influenza virus

• Has 2 types 

• Grow easily in certain cell cultures 

• produce a haemagglutinin (i.e. agglutinate red blood cells)(diagnostic)

• Frequent recombination leads to 

  • high antigenic variability 

  • pandemics 

2 types of influenza viruses

• Influenza virus A: causes major epidemics

• influenza virus B: causes milder disease; occasionally occurs in epidemics 

Clinical presentations of influenza viruses

• fever, variable respiratory symptoms

• Infants and elderly more susceptible

Diagnosis of influenza virus

Throat washings, naso-pharyngeal aspirate inoculated into cell culture

Serum of influenza virus

Paired sera (acute and convalescent stage)

Prevention of influenza virus 

• Annual vaccination especially for high risk groups

• antivirals are available for type A influenza

Parainfluenza

• Infants and young children

• Age 5-12

• Respiratory infection that could have serious complications

• Clinical presentations:

  • Croup (barking cough, high pitch sound on inhalation)

  • Bronchiolitis, bronchopneumonia

• No vaccine

Respiratory Syncytial Viruses (RSV)

• Major respiratory pathogen for children < 5 years

• Clinical presentation:

  • Pneumonia and bronchiolitis; occasionally fatal

• Epidemics

• Vaccine available

• Antiviral: Ribavizine

Rhinovirus

• Common colds

• > 100 serotypes; no cross-immunity

• Repeated infections

Coronavirus

• Member of coronaviridae family

• RNA virus

Enteric viruses 

• Enterovirus = Enteric virus

• Infect intestinal / lymphoid cells

• Poliovirus, coxsackievirus, echovirus

• Multiply in GI tract, but RARELY cause gastroenteritis

• Infection via respiratory or GI tract

• Spread to other target organs in body

• 95% inapparent infection, 4-5% minor illness, 1% serious illness

Enteroviruses

• Polioviruses

• Coxsackieviruses 

Viruses of Diarrhea

• Rotavirus

• Norovirus

Virus causing rashes 

• Measles 

• Varicella 

• Rubella

• Herpes Simplex Virus  

• Papilloma virus

Poliovirus

• Humans are the ONLY natural host

• Types 1, 2 and 3

• Causes poliomyelitis

  • Highly infectious, invades the host nervous system and can cause total paralysis in as little as a few hours

Poliovirus Diagnosis

• Isolation from stool samples (up to 5-6 weeks after infection), CSF and pericardial fluid

• Serology: acute and convalescent phases

• Carriers with inapparent infection are able to spread the disease to susceptible individuals

Polio prevention

• 2 types of Vaccination 

  • Salk vaccine 

  • Sabin vaccine 

Salk Vaccine

• Killed/inactivated vaccine; does not produce local immunity in GI of host (IgA)

• Virus can still colonize host GI tract and SPREAD to the community!!!

• used for immunocompromised

Sabin Vaccine

• Most common 

• live-attenuated host will produce IgA and IgG, so is protected against intestinal colonization and virus can NOT replicate and spread

• Oral administration

Coxsackieviruses

• Groups A and B

• Seasonal variation

• Diagnosis by stool sample and paired sera (same as polio)

• NO VACCINE

Clinical presentation of coxsackieviruses

• aseptic meningitis (both group A and B) 

• herpangina and hand-foot-and-mouth disease (group A)

• pleurodynia, pericarditis and myocarditis (group B)

  • Pleurodynia: Viruses causes muscles in ribs to squeeze and let go

Rotavirus

• Virus causing epidemics of diarrhea of infants (6mo.-2yrs), during winter months.

• The virus multiplies in the small intestine, producing a loss of fluids and electrolytes, as well as a transient malabsorption of fats and sugars.

• Highly infectious

Diagnosis of Rotavirus 

• EM or immunological testing of virus from stool samples (within 3 days)

Epidemiology of rotavirus

• Short incubation (2-3days)

• Fecal-oral route, aerosols (explosive diarrhea), fomites

• Outbreaks in daycare centres, children’s hospitals

Prevention of rotavirus

• Rapid diagnosis and isolation of patient

• Proper handwashing

• Vaccine available

Clinical manifestations of rotavirus

• acute gastroenteritis diarrhea, fever 

Norovirus

• Causes outbreaks of gastroenteritis in 18 yrs+, in any season.

• problem in cruise ships

Diagnosis of norovirus

• first exclude bacterial cause, then can be differentiated from bacterial gastroenteritis

Epidemiology of norovirus

VERY CONTAGIOUS; survives well on objects/environment – Fecal-oral route; food-borne outbreaks

Prevention of norovirus

handwashing and isolation of infected individuals

Measles

• One of the highest infectivity rates

• Lifelong immunity after natural infection +survival

• Complications: secondary bacterial infections, e.g., bronchopneumonia – Encephalitis (rare) – Exacerbation of TB and leukemia

Clinical manifestion of measles

• Koplik spots 

• rash first appears behind ears, forehead and nostrils then spreads to whole body; BLOTCHY appearance

Diagnosis of measles

• Serological

• Confirmation of Suspected Case:

  • IgM Ab in single blood specimen against measles OR a rising

  • IgG Ab titer against measles in paired blood

• Immune status

  • Circulating measles specific Ab IgG

Prevention of measles

• Immunoglobulin: can suppress disease if given within 5 days of contact with virus

• Live attenuated vaccine: very effective, widely used. Administer after 12 months of age

Rubella

• AKA German measles

• Mild disease, however extremely dangerous in non- immune pregnant women, because it can produce birth defects in the offspring.

Clinical manifestation

• similar to measles but milder

• usually enlargement of cervical, retro auricular (behind the ears) and sub-occipital lymph nodes.

• lifelong immunity 

Epidemiology and Immunity of Rubella

• pre-vaccine era, seen in school children during winter in spring, outbreaks every 7-10 years, lead to life-long immunity

• Now most cases (60%) are seen in those 15 years and older

Lab diagnosis of Rubella

• Suspected cases: detection of rubella specific IgM or rising Ab titer in paired sera

• Immunity status: detection of circulating Rubella Ab (IgG)

Prevention of congenital rubella

• Check immune status of women of childbearing age

• Diagnosis in hospitals

• Rubella serology screening of men and women starting work in hospitals

• Vaccination of non-immune

• Isolation of rubella cases in hospitals

• Vaccination is live-attenuated and is NOT admnistered to pregnant women

Varicella

• AKA chickenpox: Varicella Zoster Virus(VZV)

Clinical manifestations of varicella 

• childhood febrile illness with characteristic rash

  • Successive crops of fresh vesicles appear within 3- 4 days of onset

  • In non-immune adults, occasional pneumonia, may be fatal

• Vaccine available

Herpes Zoster (shingles)

• LIMITED rash, along trajectory of ONE nerve

• Late recurrence of latent VZV (chicken pox) infection

Prevention of varicella

vaccine; detection of susceptible persons by serological methods

Chicken pox vs. Shingles vaccine

Diagnosis of Varicella

ID of virus particles in pustules by EM or immuno methods, followed by cell culture

Herpes Simplex Virus

• Widespread

• Become LATENT after initial infection; lesions reappear periodically

• High percentage of inapparent infections

Epidemiology of HSV

• HSV1: “cold sores” oral and ocular lesions; transmitted via oral and respiratory secretions

• HSV2: “herpes genitalis” associated with genital tract; infected females can transmit to the newborn

Diagnosis of HSV

ID of virus particles by EM or immuno methods; cell cultures; Serology NOT useful

Clinical manifestation of HSV OTHER THAN cold sores

• Genital infections: recurrent in both sexes

• Herpetic encephalitis: RARE (see CNS viruses)

• Neonatal Herpes: acquired during birth from asymptomatic mother; difficult to prevent; can result in death or severe sequelae (see CNS viruses)

• Herpetic Whitlow: affects fingers, occupational hazard of health care workers; nosocomial infections in neonates

• Corneal and Conjunctival Infection: can cause ulceration of cornea and blindness

Treatment/prevention of HSV

Antivirals; C-section for symptomatic mothers; vaccines coming soon

Papilloma Virus

• Cause different types of warts

• Common warts on hands and feet

• Genital warts: sexual transmission, asymptomatic carriers

• Some types associated with cancer: cervix, vulva, penis

Diagnosis of Papilloma Virus

immuno techniques and DNA hybridization techniques; no cell cultures available

Prevention of papilloma virus

• Vaccine 

  • Gardasil 

Viruses that causes GLANDULAR ENLARGENMENT

• Mumps

• Epstein-Barr Virus 

• Cytomegalovirus (CMV)

• Hepatitis A, B, C

Mumps

• Childhood disease

• bilateral inflammation of parotid glands

• many inapparent infections

Clinical manifestations of mumps

meningitis, orchitis (can lead to sterility), ovaritis

Epidemiology of Mumps

spread by salivary and respiratory secretions; incubation 18-21 days

Prevention of Mumps

• MMR vaccine (live, attenuated)

Infectious Mononucleosis

• AKA Epstein-Barr Virus  

• Mild disease; children and young adults; can be prolonged and debilitating

• Transmission by saliva (kissing disease)

• affects lymph nodes 

• Latent virus

  • Chronic disease (rare) or asymptomatic shedding (common) for lifetime of host

• NO VACCINE

Symptoms of Epstein-Barr Virus (EBV)

lymphadenopathy, fever, sore throat, atypical lymphocytes, enlargement of liver and spleen

pathogens that affect lymph nodes

Diagnosis of EBV

• blood picture (increase in atypical lymphocytes)

• Monospot Test (detects RBC agglutination)

• Presence of EBV antigens

Cytomegalovirus (CMV)

• Herpes family, infection usually asymptomatic and latent BUT dangerous for

  • Pregnant women: neonatal infection with jaundice, enlarged liver and spleen, intellectual deficiency and motor disorders

  • Transplant patients: disseminated infection can cause transplant rejection

  • AIDS and other immunocompromised patients: frequent infection, GI tract ulceration and retinitis

Diagnosis of CMV

• Isolation of virus from urine, blood, organ biopsies (slow process, but accurate)

• CMV antigen detection, DNA hybridization and PCR in leucocytes much faster

• Serology screening for donors and recipients before transplant

Treatment/Prevention of CMV

• Match CMV immune status between donor and recipient in transplants

• Preventative administration of antivirals

• Universal precautions to prevent transmission

• NO VACCINE

Hepatitis Virus

• AKA inflammation of liver 

  • Malaise, fatigue, nausea, loss of appetite and jaundice

• Hep A, B most common and well characterized

  • Hep C, E, G less common

• Other viruses and bacteria can cause hepatitis as a complication of infection

• Diagnosis: serological

Hepatitis A

• Mainly children and young adults

• Sporadic cases and small epidemics

Epidemiology of Hep. A

• Transmission by fecal-oral route

• Incubation 15-50 days

• Stools infectious 2-3 weeks before onset

• Mild or inapparent infection in children

• No chronic hepatitis

• Life-long immunity

Diagnosis of Hep. A

• Suspected clinical cases: detection of IgM

• Immunity: detection of IgG (before travel)

Prevention of Hep. A

• Vaccine for high risk populations

• Commercial γ-globulin for prevention after exposure

Hepatitis B

Sporadic cases; all ages

Epidemiology of Hep. B

• Contaminated blood/blood products; saliva, urine, semen

• Avg. incubation 90 days

• Infective serum 30-60 days before onset of symptoms

• Carriers

Clinical Manifestation of Hep. B

• More severe than HepA

• Chronic hepatitis and chronic carrier-state

Diagnosis of Hep. B

• Blood test for HepB surface antigen (HBsAg)

• Antibodies are produced several months after onset of symptoms

  • Used as markers of infection and immunity

Prevention of Hep. B

• Universal precautions for blood and body fluids

• Proper handling of needles

• Screening

• Vaccination

• HepB immunglobulins after exposure

• HepB carriers

Hepatitis C

• Epidemiology:

  • Blood and sexual transmission

  • Initially mild disease but can cause chronic hepatitis

• Diagnosis:

  • Serological

• Prevention:

  • Same as HepB

• Treatment/cure?

  • Epclusa (sofosbuvir-velpatasvir)

Hepatitis Delta agent

• Epidemiology:

  • Blood and sexual transmission

  • “Viroid”-relies on HepB presence for replication in cells

  • Increases severity of HepB infection

• Diagnosis:

  • Serological

• Prevention:

  • Vaccination against HepB

Hepatitis E

• Transmission via fecal-oral route

• Incubation 15-50 days

• Symptoms similar to HepA BUT 20% mortality in pregnant women

• Endemic in India, Pakistan, Nepal, Burma, North Africa and Mexico

Yellow Fever Virus

• Haemorrhagic fever with hepatitis

• Endemic in Africa, South America and Caribbean

• Mortality rates as high as 50%

• Transmitted by mosquito

• Travellers to endemic countries receive live attenuated vaccine

Clinical manifestations of viruses affecting CNS

• Aseptic meningitis

• Encephalitis

• Meningo-encephalitis

• Poliomyelitis

• Slow progressive, persistant infections

General Diagnosis of viruses affecting CNS

• Always first exclude possibility of bacterial or fungal infection*

• Lumbar puncture X4

• Other specimens

  • Blood, urine, aspirates,

  • throat swabs

  • stools, sera

CNS viruses with human reservoir

• Usually an extension of a primary infection in another part of the body

  • Mumps-aseptic meningitis in children

  • Enteroviruses-aseptic meningitis in infants and children

  • HSV1-RARE cause of herpetic encephalitis in young adults

  • HSV 1 or 2-RARE cause of meningo-encephalitis in neonate or young adult

  • Vaccination for mumps, measles and polio (entero)

CNS viruses with animal reservoir

• RARE: Humans are accidental or dead-end hosts(AKA humans are not preferred host)

  • Arbovirus:

  • Rabies virus

Arbovirus

• over 200 different types

• Tropical rainforest areas

• Encephalitis

• E.g. West Nile

  • control mosquito pop. 

  • get rid of stagnant water around the house 

Rabies virus

• Fatal, acute encephalitis

• Infects mammals, transmitted via saliva

• Long incubation (30-60 days)

• Combined active and passive immunization

• Prevention by vaccination of wildlife and pets

HIV and AIDS

• Severe immunosuppressive condition; often fatal; predisposition to opportunistic infections and cancers

• HIV causes depletion in helper T-cells making the host very susceptible to other infections

• Frequent antigenic changes

HIV inactivation

Virus often protected by living inside cells, protect it from disinfecting action

Transmission of HIV

• Sexual, blood/blood products, congenital, organ transplants, sperm donation

• Lengthy asymptomatic period increases spread of disease