21-22: Human Herpesviruses

Question 1

how many human herpesviruses are there?

Answer 1

8 of them from 3 different subfamilies
- infected with 8, probably more

divided between different clades which have different features
- share commonalities, how they replicate, latency, etc.
- infect different tissues and different ways in which they cause disease

Question 2

types of human herpesviruses

Answer 2

alpha herpesviruses:
- herpes simplex virus 1 (HSV1)
- herpes simplex virus 2 (HSV2)
- varicella zoster virus (VZV)

beta herpesviruses:
- cytomegalovirus (CMV)
- human herpesvirus 6 (HHV6)
- human herpesvirus 7 (HHV7)

gamma herpesviruses:
- epstein-barr virus (EBV)
- kaposi’s sarcoma associated herpesvirus (KSHV)

Question 3

commonalities of herpesviruses

Answer 3

do not survive long outside of a host
- weak in the environment

transmission usually requires intimate direct conact
- kissing, sexual transmission, contact with contaminated fluids, etc.

Question 4

human herpesviruses latency

Answer 4

alpha herpesviruses - neuron
- infect CNS where they hide
- reactivation where virus leaves neurons and infects mucosal cells (lips for HSV1, genitals for HSV2)

beta herpesviruses - CD34+
- white blood cells constituting of T and B cells
- progenitors giving rise to T and B cells

gamma herpesviruses - B cells
- hide in plain sight since they are targeted by but hide in the immune system

Question 5

human herpesviruses seroprevalence

Answer 5

presence of antibodies in the blood will indicate exposure to herpesviruses
- different compared with things like flu, SARS-CoV-2 since antibodies would tell you you’re no longer infected

alpha herpesviruses
- HSV1 60%
- HSV2 12% (global differences, could be up to 30-40%)
- VZV 95% (only herpesvirus we have a vaccine for)

beta herpesviruses
- CMV >50%
- HHV6 90%
- HHV7 85%

gamma herpesviruses
- EBV 90%
- KSHV 10% (rises to more than 50-60% in some african countries)

vast majority where people are infected but have no/mild symptoms
- good balance between host and virus
- successful pathogen since there is little disease but efficient transmission

Question 6

symptoms of alpha herpesviruses (HSV1 and HSV2)

Answer 6

HSV1 causes sores around the mouth and lips (fever blisters/cold sores)
- can also cause genital herpes 10-30% of the time

HSV2 causes sores on or around the genitals and rectum
- can also cause oral herpes 5% of the time

sores typically resolve themselves naturally, so not life-threatening

Question 7

transmission of alpha herpesviruses (HSV1 and HSV2)

Answer 7

common viral conditions transmitted through intimate person-person contact

transmissible then areas of the skin with the virus come into contact with moist linings in certain parts of the body (mouth, vagina, anus)
- mucous membranes

HSV1: kissing, oral sex
HSV2: vaginal, anal, oral sex

Question 8

seroprevalence of alpha herpesviruses (HSV1 and HSV2)

Answer 8

3.7B under 50 have HSV1 - 60%

417M between 15 and 49 have HSV2 - 10-30%

people getting infected at young ages for HSV1 and the curve of infection rate continues

with HSV2, mainly sexual transmission so it happens later in life but increases as long as you have sex

Question 9

latency establishment of alpha herpesviruses (HSV1 and HSV2)

Answer 9

virus infects epithelial cells on mucosal surfaces, replicates, causes blisters or inapparent blisters, and infects neurons in contact with mucosal cells
- move along axons to get into cell body of neurons where they hide

75% of patients are asymptomatic

once in a while, reactivation and reinfection of mucosal cells so blisters or inapparent blisters to allow for transmission
- immune system gets a boost, clears up infection and virus goes back to hiding in neurons

can happen because of menstruation, fatigue, stress, illness, exposure to sunlight, weak immune system, etc.

Question 10

where do alpha herpesviruses establish latency? (HSV)

Answer 10

HSV1: replication in the lips, hides in neurons in the brain (trigeminal ganglia)
- virus reactivates and recedes with infection in the lips

HSV2: infection in genital mucosa, and hides in the sacral dorsal root ganglia (DRG)

Question 11

frequent asymptomatic shedding of alpha herpesviruses (HSV1 and HSV2)

Answer 11

even without lesions, release of HSV

HSV2 shedding detected in ~20% of the days in symptomatic individuals and ~10% of the days in asymptomatic infection
- most transmission happens with asymptomatic individuals since they prevent contact when symptomatic

40% have no shedding at any point even if there is a history of HSV2
- even people with no reported history of herpes shedding HSV2

Question 12

alpha herpesviruses treatment (HSV1 and HSV2)

Answer 12

hard since viruses live forever despite high immune responses
- don’t know what kind of immune response to elicit in a vaccine to have a strong response

vaccine candidates evaluated for therapeutic and preventive purposes

antivirals like acyclovir, valacyvclovir, famcyclovir
- nucleoside analogues acting as proteins that replicating viral genomes will take and incorporate into genomes, but make them stuck and prevent them from replicating further

Question 13

effect of anti-alpha herpesvirus drugs (HSV1 and HSV2)

Answer 13

incomplete suppression of lesions (~70-80%)

only ~50% reduction in transmission rate

Question 14

testing for genital herpes only recommended for people with symptoms

Answer 14

confirmation of infection

discuss future expectations

learn about available medications to manage symptoms

learn how to lower risk of infection spread

Question 15

CDC recommends against screening asymptomatic adolescents and adults for HSV

Answer 15

blood test for detection of HSV antibodies is not very accurate
- people might react to think they are infected even when they’re not (impacts their life)

cannot determine whether infection is oral/genital

no evidence that blood test would change sexual behaviour and stop spread

risk of shame and stigma outweighs potential benefits

Question 16

seroprevalence of beta herpesviruses (CMV)

Answer 16

ranges from 90% in some regions to 40-50% in others

reminder that more than 50% of people are infected with CMV

Question 17

beta herpesviruses transmission (CMV)

Answer 17

spread through body fluids
- blood, urine, saliva, breast milk, tears, semen, vaginal fluids

not casual contact

Question 18

beta herpesviruses (CMV) as generally asymptomatic

Answer 18

primary infection and reactivation generally asymptomatic
- no immune response at first so you have the most symptoms

individuals unlikely to know they are infected or shedding virus

Question 19

beta herpesviruses (CMV) in immunocompromised patients

Answer 19

most people fine but those with a weakened immune system unable to keep the virus at bay
- AIDS patients with more serious symptoms
- cancer patients where drugs kill cells replicating quickly (includes immune cells)
- organ/bone marrow transplant recipients where the immune system is wiped out, making them weak and unable to resist viral infection

serious symptoms affect eyes, lungs, liver, oesophagus, stomach and intestines

in transplant patients, graft dysfunction and rejection

Question 20

pregnant women can pass on beta herpesviruses (CMV) to their fetus

Answer 20

1 in 150 babies in the US born with CMV
- no immune system so virus can replicate

10% symptomatic, 90% asymptomatic
- some will develop long-lasting problems

CMV as the most common congenital infection in the US

Question 21

outcomes of symptomatic congenital CMV infection (beta herpesviruses)

Answer 21

permanent hearing impairment as the most common

number of severe outcomes associated with CMV infection like epilepsy, permanent visual impairment, brain abnormalities, mental retardation, premature birth/low birth weight, coordination disorders, liver/lung/spleen issues

Question 22

prevention of beta herpesviruses (CMV)

Answer 22

do not share food, utensils, drinks or straws

do not put a pacifier in your mouth

avoid contact with saliva when kissing a child

do not share a toothbrush

wash your hands

Question 23

antiviral drugs for beta herpesviruses (CMV)

Answer 23

drugs given to people infected, and also babies but a bit too late since infection happens in the fetus (wouldn’t know they are infected)

inhibit viral polymerase as nucleoside analogs
- drugs as fake blocks fooling the viral polymerase into thinking they are nucleotides
- attach to the genome being made, but do not allow continuation of the genome which cannot be further polymerised

given to immunosuppressed patients

may improve hearing and developmental outcomes for babies with signs of congenital CMV infection at birth

can have serious side effects
- affect the bone marrow and are toxic (especially to the kidney which is a common graft)

Question 24

beta herpesviruses (CMV) and vaccine development

Answer 24

ranked as the highest priority by the US institute of medicine

populations benefiting would be women of child-bearing age and transplant recipients (prior to transplantation)

Question 25

origins of gamma herpesviruses (KSHV)

Answer 25

until the early 1980s, KSHV as rare and found mainly in older men, patients with organ transplants or african men
- cancer of the skin but benign and non-aggressive

with the AIDS epidemic in 1980s, more cases of KSHV in africa and gay men with AIDS
- at the peak, 20 out of 100 homosexuals developed KSHV
- aggressive with people dying in 6 months (skin lesions and cancers spreading throughout organs and intestines)

Question 26

structure of a KSHV lesion (gamma herpesviruses)

Answer 26

long spindle cells as cancer cells

lesions develop, become sticky so RBCs get into lesions and are stuck there

Question 27

gamma herpesviruses (KSHV) caused by a virus other than HIV

Answer 27

KSHV more common if a person contracted HIV through sexual contact than other ways like blood transfusions
- other groups of people with suppressed immune systems like transplant recipients also at risk of KSHV

few agents known to increase cancer risk by 100 times, let alone 20,000 times
- strengthened the case for KSHV being caused by an infection

Question 28

discovery of gamma herpesviruses (KSHV)

Answer 28

two scientists from columbia university
- compared DNA of healthy tissue with DNA isolated from KSHV lesions

obtained two small pieces of DNA that were not human
- analysis indicated a new herpesvirus (KSHV and HHV8)

Question 29

seroprevalence of gamma herpesviruses (KSHV)

Answer 29

depends on where you live in the globe

<10% in the US, but in some regions of africa, 40-80%
- HIV epidemic still concentrated/aggressive in africa so people infected with KSHV

Question 30

gamma herpesviruses - relation between KSHV and EBV

Answer 30

EBV known and discovered before KSHV

doctor found people developing B-cell lymphomas

Question 31

gamma herpesviruses associated with cancers (KSVH and EBV)

Answer 31

EBV: mononucleosis/kissing disease (not a cancer)
- infection of B cells which release cytokines/chemokines making people tired
- lasts until the immune system can fight viral infections and control the virus

EBV: burkitt lymphoma
- again infection of B cells

EBV: nasopharynx carcinoma (epithelial cells)
- association with the presence of a co-factor which triggers it in conjunction with EBV
- a factor is preserved smoked fish

KSHV: primary effusion lymphoma (B cells)

KSHV: KS (endothelial cells)