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The Life-Cycle of HPV

The Life-Cycle of HPV

Table of Contents

Viruses aren’t living organisms but strands of DNA or RNA that make a home in other living organisms to complete their life-cycle and survive.

The life-cycle of a virus includes the process by which the virus gains entry into a living organism, how it replicates, and ultimately impacts the individual it has made a home in.

By understanding the life-cycle and how the immune system interacts with HPV, we can better understand why some strains develop into more complicated conditions like cancer.

What Makes The HPV Life-Cycle Unique?

The human papillomavirus includes a family of more than 150 subtypes that differ depending on their DNA sequences, life-cycle characteristics, and the diseases they create. HPV specifically targets the mucosal and epithelial cells and have adapted over time through evolution to infiltrate different regions of tissue and cause different diseases.

Most HPV infections occur around the mouth or genitals, with some causing visible growths like warts and others causing asymptomatic infections that take years to develop.

In addition to the type of HPV strain, symptoms that manifest also depends on the individuals’ immune system. The immune system influences how quickly the virus is cleared and whether symptoms manifest. Most HPV infections will complete their life-cycle without causing disease or symptoms at all.

Infection Stage

Infection occurs when the HPV gains entry into skin tissue, called epithelial cells. Epithelial cells line the surface of the body and can be classified into three principal shapes, squamous, columnar, and cuboidal.

When it comes to testing for HPV and cell abnormality, squamous cells are the ones that typically develop abnormalities.

Squamous cells are found in body tissue which forms the very surface of the skin. This is why during Pap smear test where a swab is used to collect surface-level cells, the squamous cells are the ones collected and examined for anything untoward.

The cells are arranged in layers that meet the rest of the body through a layer called the basement membrane. This basement layer is where the HPV virus attaches and gets internalize into the nucleus of a cell. Once the virus has entered the cell it can then use the cell’s machinery to begin replicating.

Squamous Cells Diagram
Squamous Cells Diagram

Replication:

Depending on the strain of HPV, the nature of the epithelial cells where the infection occurs, and external factors like hormones and cytokines the virus life-cycle will have different outcomes.

The virus may remain relatively silent. In this case, the virus doesn’t replicate beyond the lower layers of the basement membrane or proliferate further into the cell tissue to cause disease.

The virus may also begin to replicate, releasing its viral particles into upper epithelial layers and penetrating deeper into the mucosal lining. When the virus replicates into surrounding layers this is called a productive infection.

Productive Infections

Productive infections can be classified into grades CIN 1 (deregulated) to 3 (high-grade neoplasia). A persistent high-grade infiltration at CIN2 or CIN3 can then lead to the integration of the viral genomes into the individuals’ chromosomes and may progress into cancer.

Particular areas within the cervix lining are more susceptible to fostering cell replication than others. HPV that gain access to the transformational zone in the cervix have been linked to higher rates of cancer progression.

Two viral proteins, E6 and E7, have also been found on high-risk strains of HPV. These proteins are thought to be responsible for stimulating cell cycle entry into the upper epithelial layers and linked to cancerous changes.

Latency

In most cases, the HPV infection does not reach a cancerous state. The majority (80-90%) of HPV infections will clear on their own without clinical disease. Even with high-risk strains, the virus will likely be cleared by the local, cell-mediated immune response.

How the virus gets inactivated is through interaction with our immune system.

In a healthy immune system, active infections will initiate an immune response through CD4+ T cells. Once these cells are activated more immune molecules accumulate at the site of infiltration and overtake the viral gene expression.

A compromised or weak immune system seems to be the hallmark of HPV infections, where the failure to develop effective cell-mediated immunity to clear or control the infection results in persistent infection and increases the probability that the cells progress to cancer.

In viral latency, viral particles continue to exist within the basal layer of the epithelial cells, the virus can then get reactivated following a change in immune status.

What Makes Certain HPV Subtypes More Carcinogenic?

In order for cancer to develop, the virus has to evade immune detection over a prolonged period in order for genetic abnormalities to accumulate.

Certain subtypes of HPV, like HPV-16 and 18 are more powerful carcinogens than other strains of HPV. What makes the virus carcinogenic is its ability to persist and invade the epithelial tract for longer periods of time allowing changes in the gene expression of the underlying tissue.

It is thought that the presence of E6 and E7 proteins on high-risk strains allows for cervical intraepithelial neoplasia grade to increase from CIN 1 to 3. E6 and E7 disrupt the ability of the integrated genome to express the DNA binding protein that represses the viral entry promoter.

How Can You Assist Your Immune System?

It is clear from the research that a healthy immune system is key to preventing the HPV virus from proliferating and reaching a cancerous state.

A healthy immune system is built on a healthy diet and lifestyle. Some important factors in supporting your overall health include:

Optimizing nutrition and supplementation: Consuming fruit and vegetable-rich diet, limiting sugar and refined carbohydrate intake has been found to have a positive effect on the overall function of the immune system.

Managing psychological stress: Prolonged stress has been found to create an imbalance in the ability of the body to fight incoming infection, by over-activating areas of the immune system that exacerbate chronic illness. Engaging in daily stress management practices like meditation, exercise, and socializing can have a positive effect in improving the body’s overall resiliency.

Getting good quality sleep: Getting adequate rest, seven to eight hours of quality sleep per night, allows the immune system time to revitalize, balance hormones, and initiates cellular repair. Setting a regular bedtime, limiting caffeine intake in the afternoon, and eating a nutrient-dense diet are all ways we can improve our sleep quality.

Engaging in regular exercise and movement: From improved circulation to naturally increasing the bodies white blood cell and antibody count, staying active has a range of benefits in helping support the immune system and defense against disease. We recommend taking daily walks and engaging in bi-weekly strength training and aerobic activity.

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