L1. Viral Infections in the Blood

what are the (4) viruses infecting the blood cells?

1. EBV

2. B19V

3. HIV-1

4. HTLV-1

EBV (target + entry receptor)

Target: B lymphocytes

Entry Receptor: CD21

B19V (target + entry receptor)

Target: erythroid progenitors (RBC progenitors)

Entry Receptor: P blood antigen receptor

HIV-1 (target + entry receptor)

Target: CD4+ T cells (monocytes/macrophages/dendritic cells)

Entry Receptor: CD4+ and CCR5/CXCR4

HTLV-1 (target + entry receptor)

Target: CD4+ T cells (CD8+/monocytes/macrophages/dendritic cells)

Entry Receptor: HSPG + NRP-1 + GLUT1

viral blood infections can be transmitted by

blood transfusion + organ transplants

EBV characteristics include:

• herpes virus

• dsDNA

• enveloped

B19V characteristics include:

• parvovirus

• ssDNA

• non-enveloped

HIV-1 and HTLV-1 characteristics include:

• retroviruses

• ssRNA

• enveloped

• reverse transcriptase

which viruses are enveloped?

1. EBV

2. HIV-1

3. HTLV-1

which virus is non-enveloped?

B19V

which viruses have dsDNA?

EBV

which viruses have ssDNA?

B19V

which viruses have ssRNA?

• HTLV-1

• HIV

Epstein-Barr virus is also known as

HSV-4 (human herpesvirus 4)

Epstein-Barr virus is a

dsDNA enveloped herpesvirus

what is the prevalence of EBV?

One of the most common human viruses (9/10 of adults are seropositive)

how is EBV transmitted?

through bodily fluids, primarily saliva

primary infection of EBV is usually _____ and most people get infected in ______

• asymptomatic

• childhood

1 in 4 EBV infected teenagers develop

infectious mononucleosis (“mono”) — “kissing disease”

are there any vaccine to protect against EBV? is it a short-term or long-term infection?

• NO VACCINE

• LIFE-LONG INFECTION

EBV infects the ______ and ______

1. tonsillar epithelium

2. B lymphocytes

which cells are important in suppressing primary EBV infection?

CD8+ T cells

EBV specific antibodies

1. viral capsid — IgM

2. viral capsid — IgG

3. EBV nuclear — IgG

symptoms of EBV include: (7)

1. fatigue

2. fever

3. inflamed throat

4. swollen lymph nodes in neck

5. enlarged spleen

6. swollen liver

7. rash

do symptomatic EBV patients recover quickly?

usually yes (2-4 weeks) — however, some may continue feeling fatigued for several weeks - months

which symptomatic infection is commonly caused by EBV?

infectious mononucleosis

infectious mononucleosis symptoms include: (7)

1. fevers

2. generalized malaise

3. tonsilitis

4. pharyngitis

5. extensive, grey-white exudate

6. leukoplakia

7. cervical lymphagonopathy

infectious mononucleosis is transmitted via

saliva

EBV transmission is caused by exposure to

oropharyngeal secretions

EBV survives on an object as long as

it remains moist

EBV can also spread through ____ and _____

blood and semen

1. sexual contact

2. blood transfusion

3. organ transplantations

can you spread EBV even when asymptomatic? what happens if EBV reactivates in your system?

• YES — can spread for weeks before symptomatic

• IF REACTIVATE — can potentially infect others, regardless of when the first infection was

will EBV stay in the body or can it be completely cleared?

STAYS — remains inactive (but can be reactivated)

who can develop more severe symptoms and complications from EBV infection?

immunocompromised people

complications of EBV include: (6)

1. peri-tonsillar abscesses

2. acute bacterial sinusitis

3. suppurative lymph nodes

4. mastoiditis

5. sialadenitis

6. blockage of nasal and throat passages

EBV is also associated with these (2) conditions:

1. cancer

2. multiple sclerosis

how is EBV detected? (5)

1. atypical, cytotoxic T cells in blood smear

2. viral capsid antigen (VCA)

3. early antigen (EA)

4. EBV nuclear antigen (EBNA)

5. heterophile antibodies

anti-VCA (capsid) Ig_ appears early in EBV infection and usually disappears within _____

• IgM

• 4-6 weeks

Anti EA (early antigen) Ig_ appears in the ___ phase of EBV and falls to undetectable levels after 3-6 months

• IgG

• acute

VCA antigen associated antibody

IgM

EA associated antibody

IgG

(Match the term) Polyclonal stimulation of B cells by EBV infection results in nonspecific elevation of all immunoglobulins

heterophile antibodies

does polyclonal stimulation of B cells by EBV infection result in specific or nonspecific elevation of all immunoglobulins?

nonspecific

about _ out of 10 adults have antibodies for EBV, indicating a current or past EBV infection

9 / 10

is there a specific treatment or vaccine for EBV?

no treatment + no vaccine

management of EBV is

symptomatic — paracetamol + ibuprofen + rest + fluids + nutrition

how do you avoid spreading EBV?

• avoid kissing an infected person

• don’t share food or drinks with someone who has the virus

• don’t share personal items with an infected person

• use protection when having intercourse with someone who has the virus

• wash your hands (ya nasty)

Parvovirus B19V is also known as

erythrovirus

B19 is a

non-enveloped, ssDNA parvovirus

what is the prevalence of B19?

very common

• 30-60% of adults are seropositive

• 90% of adults >60 years old in the US are seropositive

B19 spreads through

respiratory secretions (saliva, mucus, sputum)

most people get infected with B19 during

childhood

primary B19 infection results in

flu-like symptoms, followed by erythema infectiosum

what childhood disease is associated with B19?

“fifth disease” (“slap cheek)

what disease does B19 cause in adults?

polyathralgia-artritis syndrome

can B19 be cleared in immunocompetent people?

YES — life-long antibody protection

are there any vaccines that protect against B19V infection?

NO

B19V infects ____ and ____

1. RBC progenitors

2. endothelial cells (BV wall cells)

stage 1 of B19V is characterized by

flu-like illness

stage 1 B19V symptoms

• malaise

• headache

• myalgea

• rhinorrhea

how long are stage 1 B19V patients contagious for before developing prodromal syndrome?

24-48 hours (before appearance of rash)

stage 2 of B19V is characterized by

erythema infectiosum or “fifth disease”

erythema infectiosum is also known as

fifth disease

erythema infectiosum is commonly seen in

children

stage 2 of B19V symptoms

1. nonspecific symptoms

2. distinctive rash on 5th day of infection

glove and sock syndrome

uncommon, self-limiting manifestation of B19V causing redness (erythema) and swelling (edema) of the hands and feet

clinical symptoms of “slapped cheek” disease (B19V) include

1. bright red rash on both cheeks (“slapped” appearance)

2. rash appears on trunk and spreads to arms and legs

(subsides within 1-2 weeks)

who are the (2) groups most at risk for B19V?

1. pregnant women

2. immunocompromised patients — chronic

if B19V causes reinfection in a pregnant mother (with positive B19 antibodies), are adverse effects seen in the fetus?

No

if a non-immune seronegative pregnant mother is infected with B19V, are there adverse effects seen in the fetus?

Yes — increased risk for fetal death

how does fetal death occur when a seronegative pregnant mother is infected with B19V?

B19V infection may cause severe fetal anemia —> develops symptoms of high-output cardiac failure

high output cardiac failure is also known as

hydrops fetalis

does B19V cause congenital anomalies in the fetus?

No

chronic B19 infection occurs in

immunocompromised patients (transplant, immunosuppressive therapy, HIV)

what are common manifestations of chronic B19V infection?

1. chronic anemia

2. leukopenia

3. thrombocytopenia

which (2) antibodies are useful for diagnosing erythema infectiosum caused by B19V?

1. IgG

2. IgM

which (3) lab tests can be used to detect IgG and IgM for B19V diagnosis?

1. ELISA

2. RIA (radioimmunoassay)

3. IFA (indirect fluorescent antibody)

what does a B19V seropositive result (IgG and IgM) in pregnant woman indicate?

B19V virus infection within 7 days to 4 months + possible risk to fetus

what does a positive IgG and negative IgM result (in B19V infected pregnant women) indicate?

past infection — no risk to fetus

which test can detect B19V genome in the blood?

PCR

positive B19V PCR result suggests

1. viremia

2. infection

are there any specific antiviral therapies for B19V?

No

are there any preventative measures against B19V infection?

No — but vaccine is being developed (phase I clinical trial)

HIV-1 is an

enveloped, ssRNA retrovirus

__ million people have HIV-1 worldwide and __ million people in the US have it

• worldwide — 40 million

• US — 1.2 million

HIV-1 is spread through

bodily fluids (blood, breast milk, semen, vaginal fluids)

primary HIV-1 infection presents as

flu-like symptoms followed by asymptomatic clinical latency (10-15 years)

most people get infected with HIV-1 during

adulthood

if HIV-1 is untreated, what will progress?

AIDS — acquired immunodeficiency syndrome

do people typically die from HIV-1 symptoms?

No — die due to opportunistic infections + weakened immune system

is HIV-1 infection life-long or temporary?

life-long

during acute HIV syndrome, there is (2):

1. wide dissemination of virus

2. seeding of lymphoid organs

what are the (5) stages of HIV-1 infectoin?

1. primary infectoin

2. acute HIV syndrome

3. clinical latency

4. constitutional symptoms

5. opportunistic diseases

(possibly death from AIDS + opportunistic diseases)

(T/F) ART suppresses HIV-1 to undetectable levels

True

what is the limit of ART (antiretroviral therapy)?

upon interruption of virus, the suppressed viral levels will rebound

what is the goal of ART and HAART in treating HIV-1?

1. maintaining an undetectable viral load

2. staying virally suppressed

what are the (5) kinds of inhibitors used to treat HIV-1?

1. entry inhibitors

2. reverse transcriptase inhibitors

3. fusion inhibitors

4. protease inhibitors

5. integrase strand transfer inhibitors

entry inhibitors include (3)::

1. CCR5 antagonists

2. attachment inhibitors

3. post-attachment inhibitors

reverse-transcriptase inhibitors include: (2)

1. nucleoside/nucleotide analogues

2. non-nucleoside analogues