Heartland Virus: An Emerging And Dangerous Phlebovirus

In 2009, two Missouri farmers were exhibiting symptoms of low white blood cell (leukopenia) and low blood platelet counts (thrombocytopenia) after several recent tick exposures. They were given a course of Doxycycline, however, they were not responsive to treatment. They were identified by the CDC with what we now know as Heartland Virus. Since then, there have been approximately ~40 confirmed human cases. The cases are usually allocated to southern states including Arkansas, Georgia, Illinois, Indiana, Iowa, Kansa, Kentucky, Missouri, North Carolina, Oklahoma, and Tennessee. The distribution of these cases towards southern states may be due to the main vector that carries the virus, Amblyomma americanum or the lone star tick.

Lone Star Tick

The Lone Star tick is found predominantly in the Southeast and Northeast parts of the United States, however, their distribution has been rapidly expanding due to climate change and land usage patterns. Lone Star ticks are considered an extremely aggressive tick species. They actively seek out hosts via carbon dioxide emission and vibrations. To complete their life-cycle, all ticks must take three full blood meals. The three stages of a tick include larvae, nymph, and adult, a blood meal is required to molt into each new stage. Generally, the later the stage, the greater the possibility of pathogen exposure. However, when it comes to Lone Star ticks, there is some evidence of transovarial transmission of pathogens from the mother to the offspring. So even some larvae may already be exposed to transmissible pathogens even before their first blood meals. It is important to recognize that all stages of the Lone Star ticks can be a possible threat.

Lone Star ticks are also linked to Rocky Mountain Spotted Fever, southern tick-associated rash illness (STARI), and alpha-gal syndrome (red meat allergy).

Heartland Virus

Heartland virus (HRTV) is a novel RNA Bunyaviridae Phlebovirus. The virus has been found to be genetically similar and closely related to thrombocytopenia syndrome virus (SFTSV) which is also a tick-borne phlebovirus endemic to Korea, Japan, and China. Since HRTV is a new/emerging virus, replicating it within a laboratory setting has been problematic because no mammalian host that was used was able to undergo the full stages of the virus, such as viremia. Understanding the full mechanism behind the virus is still underway.


The incubation period of Heartland virus ranges from two days to two weeks from the initial tick bite.

Commonly experienced symptoms include:

  • Fever
  • Fatigue
  • Headaches
  • Muscle aches
  • Nausea
  • Diarrhea
  • Loss of appetite
  • Bruising easily

Diagnosis And Treatment

Diagnosing Heartland virus can be difficult. Most physicians should use the following guidelines when diagnosing the illness.

An acute febrile illness (acute fever) within the last three months. Along with one of the following criteria from each group:

Epidemiologic Criteria:

  • A known tick bite, finding a tick on your body, or potential exposure to ticks through outdoor activities in the 3 weeks prior to symptom onset during spring through fall OR
  • Resides in or recently traveled to an area with previous evidence of Heartland virus.

Clinical Criteria:

  • Leukopenia (white blood cells <4,500 cells/µL) or thrombocytopenia (platelets <150,000
    cells/mL) not explained by another condition; OR
  • Suspected tick-borne disease with no response to the appropriate treatment given, such as a course of doxycycline.

Currently, no set treatment is available for Heartland virus. Most people would be treated with supportive therapy such as IV fluids, fever reducers, and pain medications. Antibiotics are NOT effective against viruses.





The mechanisms surrounding saliva proteins, glands, and their correlation to host feeding and transmission.

Tick saliva and salivary glands have long been studied regarding the effects they can induce when obtaining blood meals. 

Ticks have salivary proteins that contain immunomodulatory molecules that can affect the hosts environment, and therefore influencing blood feeding or the potential to transmit pathogens. 

Ticks have two main methods of feeding on hosts: 

1.) Pool feeding 

2.) Piercing and sucking 

  • During pool feeding, the ticks’ unique mouthparts will cut open the hosts skin and superficial vessels/capillaries which results in blood leaking. This blood is later consumed by the tick.  
  • Feeding by piercing and sucking occurs when the ticks insert their mouthparts into the skin of their host and eventually the blood vessels to take a blood meal. 

Both of these methods allow ticks to successfully acquire a blood meal and to potentially transmit any pathogens carried to their designated host. 

The saliva of ticks is made up of a few basic components;: water, ions, tick proteins/peptides, non-peptide molecules, exosomes, and host proteins. 

Some important components that ticks will inject into their host include: 

  • Anti-immunomodulatory (Immune system evasion)
  • Anti-vasodilatory (Blood vessel shrinkage)
  • Anti-coagulants (Blood clotting)
  • Anti-complement factors  (Preventing immune responses towards infections)
  • Anti-platelet aggregation factors. (Preventing blood from clotting)

Most vertebrates will react to skin injuries caused by a tick bite by forming a haemostatic plug. This “plug” closes the damaged site of the blood vessels and helps to control bleeding. Some other reactions that are seen with the initial tick bite are vasoconstriction, inflammation, and wound healing. Disabling these processes allow ticks to ensure blood flow and evasion from the hosts immune system.

Ticks are separated into two broad groups: 

  • Hard (Ixodidae) – ie;  deer, lone star, dog ticks. 
  • Soft (Argasidae) – ie; Antricola, Ornithodoros, Argas. 

The salivary glands of both groups consist of several types of acini (small sac-like cavity located within glands). 

Female ticks in the Ixodidae (hard tick) group consist of type I, II, and III acini. 

Male ticks in the Ixodidae group consist of type IV acini. 

Female and male ticks in the Argasidae (soft tick) group consist of type I, and II acini. 

  • Type I acini –  involved in osmoregulation which is maintenance by an organism of internal balance between water and dissolved materials regardless of the environmental factors. The acini aid in the absorption of humidity from a ticks environment. This is essential for maintaining the ticks reservoir or energy to engage in questing behavior when seeking out hosts. 
  • Type II and III acini – involved in synthesis protein/lipid factors, pathogen osmoregulation, development, and replication. 
  • Type IV acini – involved in salivation that contributes to the transfer of spermatophores to the females genital opening during mating. 

Recent studies show that ticks are capable of actively controlling specific types of acini through the neuropeptidergic network that stems from their synganglion (central nervous system of ticks). 



The Life-Cycle of A Tick

Ixodes scapularis is the main vector for Borrelia burgdorferi which is the causative agent of Lyme disease. Ixodes scapularis is primarily known as a woodland-associated tick, due to its natural habitat. Ixodes scapularis ticks have a 2-3 year life cycle that consist of four life stages. 

Stage 0: Mating – Mating occurs while the adult female ticks are taking a blood meal from a host. Male ticks insert their hypostome and chelicerae into the female’s genital opening and transfer spermatophores. Males can stay attached to the female throughout the 6-11 day feeding time frame. Male ticks do not take blood meals after their second stage (nymphs). Their life-cycle generally revolves around mating with females, as after mating they will die. 

Stage 1: Egg – After 14 days, multicellular eggs are expelled from the genital opening of the female. The eggs pass over the capitulum where they are coated with wax. This wax protects the eggs from drying and also binds them together into a mass. After 35 days the eggs embryonate, the body and legs of the nymph are formed. Over the next 14 days the larval will mature. Larvae seek out small hosts to whom they attach, and feed for the next 6 days. Afterwards, they drop off to molt into leaf litter to molt into their next life-stage. 

Stage 2: Larva – Larval and nymphal ticks must take a blood meal before they are able to molt into the next life stage. During this process, they may acquire dangerous pathogens, through host choice, or through co-feeding transmission. Co-feeding transmission occurs when an uninfected and infected tick feeds on the same host in close proximity. Larvae and nymphs normally feed on smaller mammals, which may include chipmunks, white-footed mice, birds, lizards, and sometimes even deer. 

Stage 3: Nymph – Nymphs emerge from larvae in roughly 28 days, however, many nymphs fail to complete the molting process and die. Peak nymph activity is highly correlated with months May, June, and July. Nymphs are considered highly dangerous due to their incredibly small size which allows them to remain incognito on various parts of a host’s body. The longer a tick remains attached to a host, the higher the chance of transmission occurring.

Stage 4: Adult  – Within 4-5 weeks nymphal ticks molt into the adult, and final stages of their life-cycle. Molting is a slow process and during this time the emerging adult ticks breathe through tubes that connect the spiracles with the exoskeleton. Adult female ticks feed on larger mammals, such as deer, humans, pets, etc. They lay a large batch of eggs, and die. Adult ticks are active specifically in the fall and spring months, however, they can show just as much activity in some of the winter months. Climbing temperatures throughout winters can create very habitable environments for ticks. As long as daytime temperatures stay above freezing and there is little snow covering the ground, tick activity can proceed as normal. Although adult female ticks may lay eggs towards the end of spring, their offspring will not begin to seek out hosts until months later.