week 3 day1: HIV, Herpes Flashcards
What part of the virus Allows attachment to host cells?
Membrane glycoP (peplomer)
What part of the virus encapsulates the genetic material? what is it made of?
Capsid, protein coat
Part of the virus that surves as an extra protective layer?
lipid envelope
4 things determining viral pathogenesis?
- Interaction with specific host cells
- Interaction with the immune system
• Immune escape
• Immune modulation or immune evasion
• Avoiding immune surveillance - Host immune response causing pathology
- Cellular transformation - cancer
What cellular product is released once our PRRs sense viral PAMPs? What are its functions?
Type 1 IFNs- - Direct anti-viral actions; Limits viral spread between cells
- increases cytotoxicity of NK and CD8 T cells
- activate signals to kill infected cells
What are the role of T cells and antibodies during a viral invasion?
Memory T cells prevent reactivation of latent virus
Antibodies neutralize virus on re-exposure
What does HIV mainly targets?
decreases CD4 T helper lymphocytes
What are the two glucoproteins of HIV and what are their functions?
gp120 - docking P, attaches to host receptor CD4, and CCR5/CXR4 coreceptor
and gp41 - fuses viral envelope to CW of the host (transmembrane glycoprotein)
What are the three structural genes of HIV and how do they contribute to HIV infection?
gag - encodes internal P
pol -encodes reverse transcriptase, viral RNA→DNA
env. -gp120(binds CT4 on T cells) and gp41 (mediates fusion of viris and cellular membrane of a host)
What do the genes responsible for regulating encode?
replication and uncoating of HIV genome and also production of virus particles
Steps of the HIV cycle?
- HIV attaches with GP120 to hosts CD4 and CCR5
- viral GP4 fuses virus with hosts CM
- Reverse transcription RNA→DNA
- Integrase helps viral DNA to integrate into hosts
- after transcription and translation protease cleaves viral polyP from host genome and mature virus exits
What are the three tests for HIV? Benefits and negatives of them?
- Antibody to envelope glycoP - takes long time for antibodies to be detectable (3-12 weeks!)
- Antigen tests - like for gag genes. Takes less time (2-6 weeks), Combo of Ag and Ab tests are rapid and now are more common
- Nucleic acid tests (PCR) - 1-4 weeks. fast but expensive, only for high risk exposure
What are the three stages of HIV infections and what are the manifestations?
- weeks 2-4 Acute HIV syndrome - wide dissemination of virus and huge dip in CD4 cells. Very infectious. Many develop Flu like symptoms
- Clinical latency - can be asymptomatic and HIV is hiding in lymph nodes. No symptoms or only mild ones. Still able to transmit to others
- AIDS - CD4 lymphocytes die out and a person is susceptible to opportunistic (most common - fungal) infections and cancer.
What are the three most common HIV co-infections?
HepB (10% of HIV patients)
Hep C (25%)
TB
What are the 8 families of Herpesviridae?
- HSV-1 Herpes simplex virus 1 - herpes labialis (cold Sores)
- HSV-2 Herpes simplex virus 2 - genital herpes
- VZV - Varicella Zoster Virus - Chicken pox, Shingles
- EBV - Epstein-Barr Virus - infectious mononucleosis, Burkitts lymphoma
- CMV - Cytomegalovirus - Congenital CMV infection
- HHV-6 Human herpesvirus -6-Roseola
- HHV-7 Human herpesvirus-7 -roseola
- KSHV - Kaposi’s sarcoma - associated Herpesvirus - Kaposi’s sarcoma
What are the group are the families HSV-1, HSV-2 and VZV associated with and what are the developmental features of that group?
Alpha Group
- short Reproductive cycle
- Efficient destruction of infected cells
- Rapid spread in culture
- latency in sensory ganglia
What are Group are the families CMV (5), HHV-6, HHV-7 associated with and what are the developmental features of that group?
Beta Group
Long reproductive cycle
Enlargement of infected cells
Slow cell-to-cell spread in culture
Multiple non-ganglionic latency sites
What are group are the families EBV, KSHV (HHV-8) viruses associated with in terms of the disease progression and developmental features?
Gamma Group
Replication in lymphoblastoid cells
Latency in lymphoid tissue (EBV),
monocytes & B lymphocytes (HHV-8)
Disease manifestation of HSV1?
Oral Herpes
•Gingivostomatitis;
herpes labialis (cold sores)
- Eye infections
- Cutaneous infections; whitlow
- Encephalitis
Can infect genitals
Disease manifestation/symptoms of HSV2?
- Genital herpes; herpes genitalis
- Neonatal infections
Can infect orally
What are some immunocompromised states that makes people more susceptible to HSV?
- Newborn infants
- Congenital immunodeficiencies (NK & TLR deficiencies, T cell > B cell)
- Acquired Immunodeficiency Syndrome
- Immunosuppressive therapy
- Transplant recipients (BMT)
- Compromised skin barriers (eczema, burns)
What is Primary Gingivostomatitis? What virus causes it? Manifestation? Incubation period? treatment?
- HSV-1 in oral mucosa of children
- Infection ranges from mild or inapparent to severe, with high fever and toxicity. Painful lesions occur on the buccal mucosa, tongue, gingiva, and pharynx
- Lesions ulcerate and resolve in 5-12 days
- Incubation: 2-10 days
- no tx, self resolve
What is herpes labialis? What virus causes it? Manifestation? What causes the recurrence? Tx?
Normal Cold Sores- Lesions (on the vermilion border of the lip) caused by HSV-1
- Recurrence often produces prodrome of itching and tingling followed by 1-2 cm vesicular lesions
- Called “fever blisters” or “cold sores”
- Heal spontaneously in 5-7 days, except in immunocompromised
- Recurrence: stress, illness, severe fatigue, & menstruation triggers
Tx: Acyclovir or Valacyclovir- prevents transmission and reoccurrences
What is Herpetic Whitlow? What virus causes it? Manifestation?
Recurrent HSV infection of finger and hand, resulting from passage of virus into break in skin caused by HSV-1 60%; HSV-2 40%
Vesicular lesions on finger become pustular, cause severe pain, loss of feeling, & prolonged morbidity
Can happen at any skin cut
Often misdiagnosed as staph and mistreated by antibiotics or incision
What is Herpetic Keratoconjunctivitis? What virus causes it? Manifestation? Tx?
Ulceration of the cornea from latent virus living in nerve cells of the skin or eye (HSV-1), or direct inoculation from lesions (HSV-1 or 2)
Occasionally deeper ulcers develop & produce stromal keratitis and blindness- dendritic ulcers
Acyclovir - topical
What is Herpes Encephalitis? Age? What virus causes it? Tx & prognosis? Can it result from primary infection?
Viral encephalitis caused by HSV 2 mostly sometimes 1 (10%)
Bimodal -Ages 10-20 and over 50
80% mortality if untreated,
Also causes Mollaret’s a rare recurring not often fatal meningitis caused by mainly HSV but sometimes other viruses
tx: IV acyclovir
Can be a result of a primary infection HSV-2 (1-3%)!
Diagnosed via CSF test
Steps of How varicella Ifection happens?
Starts with Resp. tract and conjunctiva in epithelial cells
Local replication in upper airway & regional lymph nodes
Primary viremia & infection of lymphocytes & nerve cells
Replication & secondary viremia Replication & secondary viremia
Infection of skin Infection of skin (day 10-21)
Steps of How varicella Infection happens?
Starts with Resp. tract and conjunctiva
Local replication in upper airway & regional lymph nodes
Primary viremia & infection of lymphocytes & nerve cells
Replication & secondary viremia Replication & secondary viremia
Infection of skin Infection of skin (day 10-21)
What are the Immune privileged sites?
Tissues that are in part protected from the immune system
Brain, nerves, eyes, testes, placenta/fetus
What are the risk factors for Shingles?
HIV patients
T cell dysfunction or absence in older patients
What are the symptoms of cytomegalovirus (CMV/HHV-5)? Prevalence? What disease can it cause? How is the virus shedding?
In HIV retinitis, Colitis in IBD and transplant patients
50-60% of people in US have it, 30% by age 5 100% in developing countries
Most people are asymptomatic, its easily transmittable
Most people carry it in latent phase without symptoms for life
Can cause mononucleosis (8% of mono cases)
Shedding in saliva and urine
What are the symptoms of cytomegalovirus (CMV)? What disease does it cause? How is the virus shedding?
Most people are asymptomatic, its easily transmittable
Most people carry it in latent phase without symptoms for life
Can cause mononucleosis (8% of mono cases)
Shedding in saliva and urine
replication sites of EBV KSHV (HHV-8)? Where do they stay latent?
Replication in lymphoblastoid cells
Latency in lymphoid tissue (EBV) and monocytes & B lymphocytes (HHV-8)
Symptoms of EBV? What can EBV cause?
most without symptoms
infects epithelial oropharyngeal(can cause sore throat) and then infect B cells
Then T cell activation and A-typical lymphocytes leads to enlargement of lymph nodes,liver and spleen
Its widely spread (90%) - asymptomatically shed
Can cause mononucleosis, EBV-associated malignancies
What are the two viruses mainly cause mononucleosis?
EBV, CMV and other herpesviruses
Several others can and bacteria,fungal and protozoa can contribute
What are some malignancies associated with EBV? What type of genes are expressed?
Burkitts Lymphoma, Hodgkin’s lymphoma, nasopharyngeal carcinoma, Oral hairy leukoplakia, CNS lymphoma, post transplant lymphoproliferative disease
No lytic genes only latent
Oral Hairy Leukoplakia (OHL)? What are the symptoms?
Lingual squamous epithelium, lots of replication and EBV proteins
Not premalignant.
Firm, does not scrape off with blade
What are the symptoms of KSHV (HHV-8)? What does it infect?
Classic, AIDS-related or secondary to immunosuppressants - can lead to Kaposi’s sarcoma
Infects B cells, macrophages, epithelial cells, endothelial cells, & keratinocytes
What are symptoms of Kaposi’s sarcoma? Causative agent?
Causative agent - KSHV (HHV-8)
Primary effusion lymphoma
Castleman’s disease (a lympho-proliferative disorder-overgrowth of cells in lymph nodes)
What cells does Kaposi sarcoma (HHV-8) infects?
B cells
Macrophages
Epithelial cells
Endothelial cells
Keratinocytes
