بسم الله الرحمن الرحيم

Batterjee Medical College


Virus Family Envelope Present

Capsid Symmetry

DNA Structure

Medically Important Viruses

Parvovirus No Icosahedral SS, linear B19 virusPolyomavirus No Icosahedral DS, circular,

supercoiledJC virus, BK virus

Papillomavirus No Icosahedral DS, circular, supercoiled

Human papilloma virus

Adenovirus No Icosahedral DS, linear AdenovirusHepadnavirus Yes Icosahedral DS,

incomplete circular

Hepatitis B virus

Herpesvirus Yes Icosahedral DS, linear Herpes simplex virus, varicella-zoster virus, cytomegalovirus, Epstein-Barr virus

Poxvirus Yes Complex DS, linear Smallpox virus, molluscum contagiosum virus

1SS = single-stranded; DS = double-stranded.

Classification of DNA Viruses


1-HerpesvirusesVirus Primary Infection Usual Site

of LatencyRecurrent Infection

Route of Transmission

HSV-1 GingivostomatitisVesicular lesions above

the waist

Cranial sensory ganglia

Herpes labialis, encephalitis,

keratitis

Via respiratory secretions, direct contact with virus

vesicle & salivaHSV-2 • Herpes genitalis

• Vesicular lesions below the waist

• Perinatal disseminated disease

Lumbar or sacral

sensory ganglia

Herpes genitalis Sexual contact, perinatal infection

VZV Varicella•Initial infection in oropharynx. •It spreads via blood to liver then to skin.

Cranial or thoracic sensory ganglia

Zosterreactivate years

later, in older and immuno-

compromised individuals.

Via respiratory secretions


Virus Primary Infection Usual Site of Latency

Recurrent Infection Route of Transmission

EBV •Infectious mononucleosis

•It start in pharyngeal epithelium, spreads to cervical lymph nodes, then travels via blood to liver & spleen.

B lymphocytes None Via respiratory secretions &

saliva

CMV •Congenital infection (in utero)

•Mononucleosis in transfusion recipients.

•Pneumonia & hepatitis in immuno-compromised patients

•Retinitis & enteritis, in AIDS patients

•Uncertain •Asymptomatic shedding

•Dissemination in immuno-compromised patients

•Intrauterine infection

•transfusions,•sexual contact, & secretions

HSV-8 Uncertain •Uncertain Kaposi's sarcomain AIDS patients

Sexual or organ transplantation

1-Herpesviruses


1-Herpesviruses

Herpes viruses-1


Herpesviruses

Varicella viruses


Herpesviruses

Zoster viruses


Herpesviruses

Epstein-Barr virus


Adenovirus

• Upper & lower tract respiratory disease (pharyngitis & pneumonia).

• Enteric strains cause diarrhea.

• Transmitted by respiratory droplet , iatrogenic in eye disease & fecal–oral with enteric strains.

• Live vaccine against types 3, 4, & 7 is used in military to prevent pneumonia


•Papillomas (warts); condylomata acuminata (genital warts); carcinoma of cervix & penis.

•Transmitted by direct contact of skin&genital lesion

•Two early viral genes, E6 & E7, encode proteins that inhibit activity of proteins encoded by tumor suppressor genes, p53 gene & retinoblastoma gene, respectively.

•Vaccine containing capsid proteins of four HPV types (6, 11, 16 and 18) is available.

PapillomavirusHuman Papillomavirus


PapillomavirusHuman Papillomavirus


Hepadnavirus Hepatitis B Virus

•Hepatitis B & hepatocellular carcinoma.

•Transmitted by blood, during birth & sexual intercourse.

•Hepatocellular injury due to immune attack by cytotoxic (CD8) T cells.

•Antigen–antibody complexes cause arthritis, rash, & glomerulonephritis.

•5% of HBV infections result in a chronic carrier. •Chronic hepatitis, cirrhosis & hepatocellular carcinoma can occur (integration of part of viral DNA into hepatocyte DNA).


Laboratory Diagnosis

Three serologic tests are commonly used:1- Surface antigen (HBsAg)2- Surface antibody (HBsAb)3- Core antibody (HBcAb).

•Detection of HbsAg ≥6 months chronic carrier.

•Presence of e antigen infectious chronic carrier.

•“Window" phase : HBV-infected person has neither detectable HBs antigen nor HBs antibody & diagnosed by detecting HB core antibody.



Treatment

•Alpha interferon & lamivudine reduce inflammation

associated with chronic hepatitis B but does not cure carrier

state.

Prevention

(1) vaccine that contains HBsAg as immunogen

(2)hyperimmune serum globulins obtained from donors with

high titers of HBsAb




Capsid Symmetry

RNA Structure Medically Important Viruses

Picornavirus No Icosahedral •SS linear,•nonsegmented,•positive polarity

•Poliovirus•Rhinovirus• hepatitis A virus

Hepevirus No Icosahedral •SS, linear• non-segmented• positive polarity

Hepatitis E virus

Calicivirus No Icosahedral •SS linear,•nonsegmented,•positive polarity

Norwalk virus

Reovirus No Icosahedral DS linear, 10 or 11 segments

Rotavirus

Flavivirus Yes Icosahedral •SS linear,•nonsegmented,•positive polarity

•Yellow fever virus,•dengue virus• West Nile virus,•hepatitis C virus

Togavirus Yes Icosahedral •SS linear,•nonsegmented,•positive polarity

Rubella virus

Classification of RNA Viruses


Classification of RNA Viruses

Retrovirus Yes Icosahedral SS linear, 2 identical strands (diploid), positive polarity

•HIV •human T-cell leukemia virus

OrthomyxovirusYes Helical SS linear, 8 segments, negative

polarity

•Influenza virus

Paramyxovirus Yes Helical SS linear, nonsegmented, negative polarity

•Measles virus,• mumps virus,•respiratory syncytial virus

Rhabdovirus Yes Helical SS linear, nonsegmented, negative polarity

•Rabies virus

Filovirus Yes Helical SS linear, nonsegmented, negative polarity

• Ebola virus• Marburg virus


Capsid Symmetry

RNA Structure Medically Important Viruses


• Range of responses to poliovirus infection includes:

(1) inapparent, asymptomatic infection

(2) abortive poliomyelitis

(3) nonparalytic poliomyelitis

(4) paralytic poliomyelitis.

• Transmission by fecal–oral route & humans are natural

reservoir.

• Virus replicates in pharynx & GI tract & spread to local

lymph nodes & then through blood to CNS.

PicornavirusEnteroviruses: Poliovirus


• Most infections are asymptomatic or very mild.

• Aseptic meningitis is more than paralytic polio.

• Paralysis is the result of death of motor neurons, anterior

horn cells in the spinal cord.

• Virus in spinal fluid indicates CNS infection .

• Virus in stools indicates infection ( not necessarily disease) as it is found in GIT of asymptomatic carriers.



• Disease can be prevented by:

- Salk: inactivated vaccine

- Sabin: live, attenuated vaccine

both induce humoral antibody that neutralizes virus in bloodstream.

Sabin vaccine has been preferred vaccine as :

• Oral vaccine

• Induces intestinal IgA, that prevent GIT infection

• Induces immunity of longer duration



• Hepatitis A.

•Transmission by fecal–oral route. Blood-borne transmission is uncommon because viremia is brief & of low titer.

•Virus replicates in GIT then spreads to liver during brief viremic period.

•Virus is not cytopathic for hepatocyte & hepatocellular injury is caused by immune attack by cytotoxic T cells.

•Vaccine contains killed virus. Administration of immune globulin during incubation period

PicornavirusEnteroviruses: Hepatitis A Virus


• It causes the following diseases:

-Aseptic meningitis, Myocarditis, pericarditis

-Herpangina (fever, sore throat & tender vesicles in oropharynx)

-Pleurodynia (fever & severe pleuritic-type chest pain due to an infection of the intercostal muscles not of pleura

- Hand, foot &mouth disease (vesicular rash on hands & feet & ulcerations in mouth, mainly in children).

- Coxsackie virus B4 may cause juvenile diabetes

• Transmission by fecal–oral route.

• Initial site of infection is oropharynx, but main site is GI tract then spreads through blood to various organs.

PicornavirusEnteroviruses:Coxsackie Viruses


• Common cold.

•There are more than 100 serotypes,which explains why the common cold is so common.

•They are destroyed by stomach acid

•Transmission by aerosol droplets &

hand-to-nose contact

•Infection is limited to mucosa of upper respiratory tract & conjunctiva.

•Virus replicates best at low temperatures of nose & less well at 37°C.

PicornavirusRhinoviruses


• Influenza. Influenza A cause worldwide epidemics.

• It has two major antigens ; hemagglutinin (HA) &

neuraminidase (NA) on separate surface spikes.

• Antigenic shift in these proteins as a result of reassortment

of RNA segments accounts for the epidemics of influenza

• Antigenic drift due to mutations

also contributes.

Influenza Virus

Orthomyxovirus


• Antigenicity of internal nucleocapsid protein determines virus is A, B or C influenza virus.

• Transmission by respiratory droplets.

• Infection limited to epithelium of respiratory tract.

• Neuraminidase inhibitor, oseltamivir (Tamiflu, drug of choice) & Zanamivir is used in treatment.

OrthomyxovirusInfluenza Virus


Two types of vaccines are available:

1-killed (subunit) vaccine:

purified HA & NA.

2- Live, temperature-sensitive mutant of influenza virus.

The virus replicates in cool nasal passages & induces

secretory IgA, but not in warm lower respiratory tract.

OrthomyxovirusInfluenza Virus


• Measles & Subacute sclerosing panencephalitis.


• Initial site of infection is upper respiratory tract & spreads to local lymph nodes then via blood to other organs & skin.

• Maculopapular rash is due to cell-mediated immune attack by cytotoxic T cells on virus-infected vascular endothelial cells in the skin.

• Vaccine contains live, attenuated virus, given in combination with mumps & rubella vaccines.

ParamyxovirusMeasles Virus


•Mumps. Bilateral orchitis & sterility is rare

•Transmission by respiratory droplets.

• Initial site of infection is upper respiratory tract & spreads to local lymph nodes then via blood to other organs, especially the parotid glands, testes, ovaries, meninges & pancreas.

•Vaccine contains live, attenuated virus, given in combination with measles and rubella vaccines

ParamyxovirusMumps Virus


• Bronchiolitis &pneumonia in infants & otitis media in older

children.


ParamyxovirusRespiratory Syncytial Virus

ParamyxovirusParainfluenza Virus

• Bronchiolitis in infants, croup in young children & common

cold in adults.



TogavirusRubella Virus

• Rubella & Congenital rubella syndrome (congenital malformations, affecting cardiovascular & CNS)

• Transmission by respiratory droplets & across the placenta from mother to fetus (during first trimester)

• Initial site of infection is nasopharynx, then to local lymph nodes & disseminates to skin via blood. Rash due to viral replication & immune injury.

• Vaccine contains live, attenuated virus, given in combination with measles and mumps vaccine.


• Common cold & SARS (severe acute respiratory

syndrome).


• It Infects mucosal cells of respiratory tract.

CoronavirusCoronavirus


• Rabies (encephalitis)

• Transmission by animal bite & aerosols of bat saliva.

• Viral receptor is the acetylcholine receptor.

• Replication of virus at site of bite, followed by axonal transport up nerve to CNS then replicating in brain & migrates to salivary glands & saliva.

• Tissue stained with fluorescent • antibody to detect cytoplasmic • inclusions (Negri bodies).

RhabdovirusRabies Virus


•Preexposure prevention: Rabies vaccine

•Postexposure prevention:

1.Washing wound

2.Giving rabies immune globulins (passive

immunization) into wound

3.Giving inactivated vaccine (active immunization)

made in human cell culture.

RhabdovirusRabies Virus


• Outbreaks of hepatitis in developing countries.

• Similar to hepatitis A virus in the following ways:

- Transmitted by fecal–oral route

- No chronic carrier state

- No cirrhosis

- No hepatocellular carcinoma.

HepevirusHepatitis E Virus


• Gastroenteritis (watery diarrhea).

• Transmission by Fecal–oral route.

• Infection is limited to the mucosal cells of the

intestinal tract.

CalicivirusNorwalk Virus (Norovirus)


• Gastroenteritis (diarrhea) in young children.

• Rotavirus is resistant to stomach acid

• Transmission by the fecal–oral route.

There are two rotavirus vaccines.

• Live attenuated vaccine contains single most

common rotavirus serotype (G1)• Live reassortant vaccine contains 5 rotavirus strains.

ReovirusRotavirus


•Hepatitis C & hepatocellular carcinoma. •Transmission is via blood. Sexual transmission & from mother to child probably occurs.

•Hepatocellular injury caused by cytotoxic T cells & HCV does not cause a cytopathic effect.

•50% of infections result in chronic carrier which predisposes to chronic hepatitis & hepatocellular carcinoma.

FlavivirusHepatitis C Virus


• Serologic testing detects antibody to HCV. • PCR-based assay for "viral load" can be used to evaluate whether active infection is present.

• Alpha interferon plus ribavirin mitigates chronic hepatitis but does not eradicate carrier state.

• Posttransfusion hepatitis can be prevented by detection of antibodies in donated blood.

FlavivirusHepatitis C Virus


• Hepatitis D (hepatitis delta).• Defective virus that uses HBs Ag as its protein coat &

replicate only in cells infected with HBV (HBV is helper virus).

• Transmitted by blood, sexually & from mother to child.• Hepatocellular injury caused by cytotoxic T cells.• Chronic hepatitis & chronic carrier state occur.• Treatment by Alpha interferon mitigates symptoms but

does not eradicate carrier state.• HBV vaccine & HBV hyperimmune globulins will

prevent HDV infection also.

DeltavirusHepatitis D Virus


RetrovirusHuman Immunodeficiency Virus

•Acquired immunodeficiency syndrome (AIDS).

•RNA-dependent DNA polymerase (reverse

transcriptase) makes a DNA copy of the genome,

which integrates into host cell DNA.

•Precursor polypeptides cleaved by virus–encoded

protease to produce functional viral proteins.

•Antigenicity of gp120 protein changes rapidly

there are many serotypes.


• Transmission by body fluids, e.g., blood & semen,

transplacental & perinatal transmission.

Two receptors are required for HIV to enter cells:

1 - CD4 protein :

it is found on helper T cells. HIV infects and kills

helper T cells, which predisposes to opportunistic

infections.

2 - chemokine receptor such as CCR5.



•Detecting antibody with ELISA as screening test

and Western blot as confirmatory test.

•Determine the "viral load," i.e., the amount of HIV

RNA in the plasma, using PCR-based assays.

•High viral load predicts more rapid progression to

AIDS



Treatment

• Highly active antiretroviral therapy (HAART)

consists of two nucleoside inhibitors (inhibit HIV

replication by inhibiting reverse transcriptase) &

one protease inhibitor (prevent cleavage of

precursor polypeptides).

• Clinical improvement occurs, but virus persists.



• Screening of blood prior to transfusion for the presence of antibody.

• "Safe sex," including the use of condoms.

• Nucleoside inhibitors (zidovudine) with or without a protease inhibitor should be given to HIV-infected mothers and their newborns.

• Nucleoside inhibitors (Zidovudine & lamivudine ) & protease inhibitor should be given after a needle-stick injury.



Family GenusViruses of Medical Interest

Togavirus Alphavirus•Eastern equine encephalitis virus•western equine encephalitis virus

Flavivirus Flavivirus•St. Louis encephalitis virus• Yellow fever virus• Dengue virus, •West Nile virus

Bunyavirus BunyavirusCalifornia encephalitis virus

Reovirus OrbivirusColorado tick fever virus

Classification of Major Arboviruses

Arboviruses

All arboviruses are transmitted by arthropods (arthropod-borne) such as mosquitoes & ticks from the wild animal reservoir to humans.


• Yellow fever

• "Jungle" yellow fever is transmitted from monkeys to

human by mosquitoes.

• "Urban" yellow fever is transmitted from human (reservoir)

to human by Aedes mosquitoes

• It is severe, life-threatening disease characterized by

jaundice & fever.

• It begins with sudden onset of fever, headache, myalgias, &

photophobia.

• There is a live, attenuated vaccine for humans.

ArbovirusesFlavivirus: Yellow Fever Virus


• Dengue fever.

• Transmitted by Aedes mosquitoes from one human to

another.

• Classic dengue (worldwide) (breakbone fever) begins

suddenly with influenzalike syndrome consisting of fever,

malaise, cough, & headache.

• Severe pains in muscles & joints (breakbone) occur.

• Enlarged lymph nodes, maculopapular rash & leukopenia

• After a week, symptoms regress but weakness may persist.

ArbovirusesFlavivirus: Dengue Virus


The diagnosis : Isolation of virus in cell culture & Serologic

tests that demonstrate presence of: IgM antibody & fourfold

or greater rise in antibody titer in acute & convalescent sera.

ArbovirusesFlavivirus: Dengue Virus

Outbreaks are controlled by using:

• Insecticides

• Raining stagnant water serves as breeding place for

mosquitoes

• Personal protection includes: Using mosquito repellent &

Wearing clothing that covers the entire body.


• Creutzfeldt-Jakob disease (CJD), variant CJD & kuru (transmissible spongiform encephalopathies)

• There is a hereditary form of CJD called Gerstmann-Sträussler-Scheinker (GSS) syndrome.

• Prions are composed of protein only.

• They have no detectable nucleic acid & highly resistant to UV light, formaldehyde & heat.

• They are encoded by a cellular gene.

Prions


• Pathogenic form (beta-pleated sheet) increases in amount by inducing conformational change in normal form (alpha helix).

• In GSS syndrome, a mutation occurs that enhances conformational change to beta-pleated sheet form.

• CJD is transmitted by pituitary extracts, brain electrodes & corneal transplants.

• Kuru was transmitted by ingestion or inoculation of human brain tissue.

• Variant CJD is transmitted by ingestion of cow brain tissue in undercooked food

Prions


• Aggregation of prion filaments within neurons

occurs, vacuoles within neurons cause spongi-

form changes in brain, no inflammation or immune

response occurs.

• Brain biopsy shows spongiform changes.

• Prions cannot be grown in culture.

Prions

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