21-22: Human Herpesviruses Flashcards
how many human herpesviruses are there?
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
types of human herpesviruses
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)
commonalities of herpesviruses
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.
human herpesviruses latency
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
human herpesviruses seroprevalence
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
symptoms of alpha herpesviruses (HSV1 and HSV2)
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
transmission of alpha herpesviruses (HSV1 and HSV2)
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
seroprevalence of alpha herpesviruses (HSV1 and HSV2)
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
latency establishment of alpha herpesviruses (HSV1 and HSV2)
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.
where do alpha herpesviruses establish latency? (HSV)
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)
frequent asymptomatic shedding of alpha herpesviruses (HSV1 and HSV2)
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
alpha herpesviruses treatment (HSV1 and HSV2)
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
effect of anti-alpha herpesvirus drugs (HSV1 and HSV2)
incomplete suppression of lesions (~70-80%)
only ~50% reduction in transmission rate
testing for genital herpes only recommended for people with symptoms
confirmation of infection
discuss future expectations
learn about available medications to manage symptoms
learn how to lower risk of infection spread
CDC recommends against screening asymptomatic adolescents and adults for HSV
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
seroprevalence of beta herpesviruses (CMV)
ranges from 90% in some regions to 40-50% in others
reminder that more than 50% of people are infected with CMV
beta herpesviruses transmission (CMV)
spread through body fluids
- blood, urine, saliva, breast milk, tears, semen, vaginal fluids
not casual contact
beta herpesviruses (CMV) as generally asymptomatic
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
beta herpesviruses (CMV) in immunocompromised patients
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
pregnant women can pass on beta herpesviruses (CMV) to their fetus
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
outcomes of symptomatic congenital CMV infection (beta herpesviruses)
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
prevention of beta herpesviruses (CMV)
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
antiviral drugs for beta herpesviruses (CMV)
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)
beta herpesviruses (CMV) and vaccine development
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)
origins of gamma herpesviruses (KSHV)
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)
structure of a KSHV lesion (gamma herpesviruses)
long spindle cells as cancer cells
lesions develop, become sticky so RBCs get into lesions and are stuck there
gamma herpesviruses (KSHV) caused by a virus other than HIV
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
discovery of gamma herpesviruses (KSHV)
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)
seroprevalence of gamma herpesviruses (KSHV)
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
gamma herpesviruses - relation between KSHV and EBV
EBV known and discovered before KSHV
doctor found people developing B-cell lymphomas
gamma herpesviruses associated with cancers (KSVH and EBV)
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)
