Dna viruses

• DNA viruses replicate in the nucleus, except for Poxvirus, which replicates in the cytoplasm
• DNA viruses are double-stranded, except for Parvovirus, which is single-stranded

Hepadnaviridae

• Hepatitis B virus is a dsDNA enveloped virus
• Hepatitis B is transmitted via needles, sexual contact, and across the placenta
• The incubation period for Hepatitis B is 70-100 days
• Hepatitis can be acute or chronic, with chronic carriers potentially developing hepatic cancer
• Treatment includes antivirals like Lamivudine, Adefovir, Telbivudine, and Entecavir, as well as Interferon alpha
• Hepatitis B vaccine is available for prevention

Hepatitis B Terminology and Markers

• HBsAg is a surface antigen found during acute disease and persistent infections; presence past 6 months indicates chronic infection
• HBsAb is an antibody to the surface antigen that provides immunity to HBV
• HBcAg is the HBV core antigen
• HBcAb is an antibody to the HBV core antigen and the first antibody to appear; IgM antibody to core is an important test for recent infection
• HBeAg is a second antigenic determinant in the core of the virus correlating with active viral production and infectivity
• HBeAb is an antibody to HBeAg, generally detectable after the virus is no longer detectable, and suggests a lower risk of transmission

Hepatitis

• Hepatitis involves liver inflammation
• Symptoms include jaundice, abdominal pain, fatigue, nausea, vomiting, and appetite loss, and may occur years after initial infection
• The host immune response is responsible for much of the liver damage
• Diagnosis includes observation of jaundice, enlarged liver, or fluid in the abdomen
• Serological testing is performed to test for the surface antigen or antibodies formed against Hepatitis B virus antigens

Herpesviridae

• Herpesviridae are dsDNA enveloped viruses
• HSV 1 causes oral lesions and affects the brain and eyes
• HSV 2 causes genital lesions
• HHV 3 is Varicella Zoster Virus which causes chicken pox and shingles
• HHV 4 is Epstein Barr Virus which causes mononucleosis and Burkitt’s lymphoma
• HHV 5 is Cytomegalovirus and is found in the immunosuppressed
• HHV 6 causes Roseola or Exanthem subitum
• HHV 8 causes Kaposi Sarcoma

HSV-1 (Herpes Simplex Virus 1)

• HSV-1 infection often occurs in infancy and is transmitted orally/respiratory
• It remains latent in the trigeminal ganglia
• Lab studies involve Tzanck smear
• Multinucleated giant cells are typically found at the base of herpesvirus lesions
• Treatment is Acyclovir
• HSV-1 causes diseases such as acute gingivostomatitis, recurrent herpes labialis (cold sores), keratoconjunctivitis (keratitis), encephalitis, and herpetic whitlow
• Recurrence is triggered by excessive UV exposure, emotional stress, and hormonal changes (menstruation)
• Complications include herpetic keratitis (cornea) and herpes encephalitis (brain)

HSV-2(Herpes Simplex Virus 2)

• Herpes Simplex Virus 2 (HSV-2) causes genital herpes
• Incubation period is approximately one week
• Symptoms in both males and females include primary vesicular lesions that break down to form painful ulcers and burning, painful urination
• It is most infectious when lesions are present
• HSV-2 also causes neonatal encephalitis and other forms of neonatal herpes, and aseptic meningitis
• Latency occurs in the sacral ganglia
• Recurrences are triggered by menstruation, emotional stress, illness, and fever
• Complications include neonatal herpes, which can cross the placental barrier or be transmitted to the baby during birth, encephalitis, ophthalmic herpes, and whitlow
• Neonatal herpes can result in spontaneous abortion, mental retardation, vision and/or hearing damage
• Lab studies use Tzanck smear
• Multinucleated giant cells are typically found at the base of herpesvirus lesions
• Treatment involves Acyclovir and Valacyclovir

HHV-3 (Varicella-Zoster Virus - VZV)

• HHV-3 (Varicella-Zoster Virus - VZV) is transmitted via the respiratory route
• Initial infection induces immunity, enters latency, and is more serious if infected at adult-age
• Symptoms of chickenpox include malaise and fever prior to rash
• Symptoms include a rash mostly on the face and trunk that is maculopapular then vesicular, and lesions form a crust, which co-exists with new lesions
• Chickenpox may involve mucous membranes
• Affected individuals are contagious 48 hours before the rash until all lesions are crusted
• Acyclovir is used for treatment
• A live attenuated vaccine (varivax) is available for prevention

Varicella-Zoster Virus Latency

• Varicella-zoster virus is latent in the dorsal root ganglion near the spine
• Recurrence of chickenpox is shingles; also known as Herpes Zoster
• Vesicles is noted along the dermatome of a thoracic nerve
• Diagnosis is by Tzanck Smear
• Multinucleated giant cells are seen
• Antigen detection is by PCR
• Acyclovir is used for treatment
• Prevention is by recombinant vaccine (Shingrix)

HHV 4 Epstein-Barr Virus

• Incubation is 4-7 weeks
• EBV multiplies within B cells
• Transmission occurs often during childhood or adolescence via kissing disease (saliva, blood, semen)
• The disease caused by EBV is Infectious mononucleosis ("mono")
• Symptoms include sore throat, fever, swollen neck lymph nodes, and general weakness
• It is usually self-limiting, and infection results in immunity
• Characterized by heterophile-positive mononucleosis
• Can lead to X-linked lymphoproliferative syndrome in immunocompromised patients and Hairy Oral leukoplakia in AIDS patients
• Lab Studies show atypical lymphocytes
• Positive monospot test results
• Treatment is self-limiting and typically resolves in about a month
• EBV is isolated from tumors of Burkitt's lymphoma
• Burkitt's Lymphoma turns malignant in patients who become infected with EBV who are HIV positive
• EBV has oncogene properties via the gene named c-myc, this drives cell growth in large quantities causing cancer
• Burkitt's Lymphoma is treated with chemotherapy

HHV 5 Cytomegalovirus

• Transmission occurs via body fluids such as saliva, semen, breast milk, kissing, sexual contact, transfused blood, and transplanted tissue
• CMV remains latent in monocytes
• Cells have distinct 'inclusion bodies' visible by microscopy, called owl's eye inclusions
• Infected cells swell in size
• CMV is a common opportunistic pathogen, typically present in people, but reactivates when the host becomes immunocompromised
• Primary CMV infection during pregnancy (crosses placenta) causes cytomegalic inclusion disease, and serious damage to fetus can result
• Damage includes severe mental retardation, jaundice, hearing loss, enlarged liver and spleen (hepatosplenomegaly), thrombocytic purpura (“blueberry muffin baby")
• Other infections by CMV include pneumonia, mononucleosis (negative monospot), retinitis, and esophagitis
• Infections have heterophile negative mononucleosis
• Diagnosis occurs via lab studies showing owl’s eye inclusions
• Treatment is with gangciclovir in immunocompromised individuals

HHV 6 Roseola

• Transmission occurs via respiratory droplets
• Pathogenesis replicates in peripheral blood mononuclear cells
• Symptoms include runny nose, sore throat, cough, and high fever (39.4 °C)
• Maculopapular rash appears on chest and abdomen a few days after fever subsides; not vesicular
• Roseola infantum (exanthem subitem) is a disease
• Diagnosis is clinical via observation of symptoms
• Treatment is symptomatic

HHV 8 Kaposi's Sarcoma-Associated Herpesvirus

• Transmission occurs through sexual contact, saliva, vertical transmission, and transplantation
• Causes purple red (port wine) raised lesions
• Kaposi’s Sarcoma is cancer of endothelial cells causing blood vessels to proliferate
• Seen in HIV/AIDS and transplant patients
• Treatment includes radiation and chemotherapy

Adenoviridae

• Adenoviridae have a dsDNA non-enveloped structure
• Transmission occurs via direct contact, respiratory route, and fecal-oral route
• Diseases caused by Adenovirus include pharyngitis, conjunctivitis (non-purulent), pneumonia, and acute hemorrhagic cystitis
• Treatment is self-limiting

Adenovirus-related Diseases

• Serotypes are associated with specific syndromes
• Type 3, 4, 7, and 21 cause respiratory diseases
• Types 8 and 19 cause keratoconjunctivitis
• Types 11 and 21 cause hemorrhagic cystitis
• Types 40 and 41 cause infantile gastroenteritis

Poxviridae

• Poxviridae have dsDNA enveloped structure
• Transmission is via respiratory droplets and direct contact
• Diseases include smallpox, which presents with a rash and flu-like symptoms
• Other diseases include molluscum contagiosum, which causes epidermal growth (flesh colored dome with central umbilicated dimple), and monkey pox
• Treatment is self-limiting, with cryotherapy for molluscum lesions

Papillomaviridae

• Human Papillomavirus is dsDNA non-enveloped
• Transmission is via direct contact
• 200 strains of HPV are found and 14 are oncogenic
• Diseases include common warts (type 2&4), plantar warts (type 1), and anogenital warts (types 6 & 11)
• Cervical cancer (types 16, 18, 30’s) occurs due to inactive tumor suppressor genes (p53 and Rb)
• Oropharyngeal, anal, vaginal, vulvar, and penile cancer is possible

HPV

• Diagnosis through lab studies involves koilocytic cells seen on pap smear
• Cryotherapy is a treatment for skin warts
• Topical imiquimod or podophyllin is used for the treatment of genital warts
• Prevention involves the VACCINE Gardasil 9, which protects against types 6, 11, 16, and 18

Polyomaviridae

• Polyomaviridae contain dsDNA and are non-enveloped
• BK virus infection usually occurs during early childhood
• Evidence of specific antibody is found in 70-80% of adult sera
• Virus may persist in kidneys and lymphoid tissues after primary infection
• Transmission is through the respiratory tract
• It establishes latent infection in the kidney
• Diseases include hemorrhagic cystitis in bone marrow transplant recipients and polyomavirus-associated nephropathy in renal transplant recipients and AIDS patients
• JC Virus also causes infection during early childhood.
• Transmission occurs through the respiratory tract
• Reactivation may occur when the host's immune response is impaired, such as by renal transplantation, during pregnancy, or with increasing age
• Diseases include JC virus causing Progressive multifocal leukoencephalopathy (PML), a fatal brain disease especially in immunocompromised people with HIV
• It damages white matter in the brain
• Treatment is supportive only

Parvoviridae

• Parvoviridae have ssDNA and are non-enveloped
• The reservoir is the human respiratory tract
• Transmission is via respiratory droplets, fomites, and placenta
• Parvovirus enters progenitor erythrocytes, replicates and lyses them afterwards
• Parvovirus is related to diseases caused by Parvovirus B19 - Fifth Disease or Erythema Infectiosum causes cold-like symptoms followed by a "slapped-cheek face rash” in children which then spreads; adults experience joint pain and swelling with no rash - Hydrops Fetalis causes RBC destruction and inhibition of RBC formation, leading to death of the fetus in pregnant women - Anemia is found in sickle cell patients
• Diagnosis is through serology and molecular analysis
• Treatment is self-limiting and supportive