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CURATOR
A pinboard by
Aayushi Uberoi

PhD candidate at University of Wisconsin and study the role of papillomaviruses in skin cancer

PINBOARD SUMMARY

You sure want to use that sunscreen!

I work on everyone’s favorite embarrassing topic - Warts.

A very reliable therapy, according to Louisiana Voodoo, is that if you rub a potato on a wart, burry the potato, the wart will go away. If only that’s how viruses worked!

Warts (also referred to as papillomas) - are caused by a really small, cancer-causing virus, called the human papillomavirus or HPV. There are more than 140 sub-types of HPVs that can cause genital or skin warts that can, in some instances, progress to cancer. The HPV-vaccine protects us from at least 6 types of HPVs that cause genital cancer. What about the remaining 134 types? And that’s where my thesis comes in – I am trying to understand the biology of skin-related HPVs and how they cause cancers?

Research progress has been hampered primarily because HPVs are species specific! So a human papillomavirus infects only humans and a porcupine papillomavirus, that actually does exist, infects only a porcupine. When I started my PhD, the first ever papillomavirus that could infect a mouse was discovered. After all these years, we can now study a papillomavirus infection in a mouse model.

In my thesis work, I learnt something unique about MusPV – It caused skin warts only in animals genetically modified to have defective immune system. And absolutely no disease in animals with an intact immune system. In one of my experiments, I exposed virus-infected mice with a healthy immune system, to UV- the same ultraviolet radiation spectra found in the sunlight. Now these healthy mice that did not develop disease previously, started getting warts and in some cases even cancer.

This was a significant observation as it has been hypothesized for years, that individuals chronically exposed to sunlight may develop HPV-associated skin cancers. But no-one really understands why? So with this UV-infection model in mice I have now discovered that UV actually causes defects in the immune system of these mice preventing them to fight off the infection.

So how does my thesis fit in the big picture: by understanding the mechanism of disease we can develop a therapy for skin cancers. I’m hopeful that very soon we will be able to build a vaccine that can prevent skin cancers due to HPVs.

7 ITEMS PINNED

The human skin double-stranded DNA virome: topographical and temporal diversity, genetic enrichment, and dynamic associations with the host microbiome.

Abstract: Viruses make up a major component of the human microbiota but are poorly understood in the skin, our primary barrier to the external environment. Viral communities have the potential to modulate states of cutaneous health and disease. Bacteriophages are known to influence the structure and function of microbial communities through predation and genetic exchange. Human viruses are associated with skin cancers and a multitude of cutaneous manifestations. Despite these important roles, little is known regarding the human skin virome and its interactions with the host microbiome. Here we evaluated the human cutaneous double-stranded DNA virome by metagenomic sequencing of DNA from purified virus-like particles (VLPs). In parallel, we employed metagenomic sequencing of the total skin microbiome to assess covariation and infer interactions with the virome. Samples were collected from 16 subjects at eight body sites over 1 month. In addition to the microenviroment, which is known to partition the bacterial and fungal microbiota, natural skin occlusion was strongly associated with skin virome community composition. Viral contigs were enriched for genes indicative of a temperate phage replication style and also maintained genes encoding potential antibiotic resistance and virulence factors. CRISPR spacers identified in the bacterial DNA sequences provided a record of phage predation and suggest a mechanism to explain spatial partitioning of skin phage communities. Finally, we modeled the structure of bacterial and phage communities together to reveal a complex microbial environment with a Corynebacterium hub. These results reveal the previously underappreciated diversity, encoded functions, and viral-microbial dynamic unique to the human skin virome.To date, most cutaneous microbiome studies have focused on bacterial and fungal communities. Skin viral communities and their relationships with their hosts remain poorly understood despite their potential to modulate states of cutaneous health and disease. Previous studies employing whole-metagenome sequencing without purification for virus-like particles (VLPs) have provided some insight into the viral component of the skin microbiome but have not completely characterized these communities or analyzed interactions with the host microbiome. Here we present an optimized virus purification technique and corresponding analysis tools for gaining novel insights into the skin virome, including viral "dark matter," and its potential interactions with the host microbiome. The work presented here establishes a baseline of the healthy human skin virome and is a necessary foundation for future studies examining viral perturbations in skin health and disease.

Pub.: 23 Oct '15, Pinned: 16 Aug '17

Natural history of cutaneous human papillomavirus (HPV) infection in men: the HIM study.

Abstract: Accumulating evidence suggests that cutaneous human papillomavirus (HPV) infection is associated with non-melanoma skin cancer (NMSC). Little is known about the natural history of cutaneous HPV. A sub-cohort of 209 men with no NMSC history, initially enrolled in the HPV infection in men (HIM) study, were followed for a median of 12.6 months. Epidemiological data were collected through self-administered questionnaires. Cutaneous HPV DNA was measured in normal skin swabs (SS) and eyebrow hairs (EB) for 25 and 16 HPV types in genera β and γ, respectively. Any β HPV infection was more prevalent in SS (67.3%) compared to EB (56.5%, p = 0.04). Incidence in SS was higher than 20 per 1,000 person-months for HPV types 4, 5, 23, 38 and 76. Median duration of persistence of β and γ HPV infection was 8.6 and 6.1 months in EB, respectively, and 11.3 months and 6.3 months, in SS, respectively. Older age (>44 years vs. 18-30 years) was significantly associated with prevalent (SS OR = 3.0, 95% CI = 1.2-7.0) and persistent β HPV infection (EB OR = 6.1, 95% CI = 2.6-14.1). History of blistering sunburn was associated with prevalent (OR = 2.8, 95% CI = 1.3-5.8) and persistent (OR = 2.3, 95% CI = 1.2-4.6) β HPV infection in SS. Cutaneous HPV is highly prevalent in men, with age and blistering sunburn being significant risk factors for cutaneous β HPV infection.

Pub.: 10 Sep '14, Pinned: 15 Jul '17

The Skin Microbiome: Is It Affected by UV-induced Immune Suppression?

Abstract: Human skin apart from functioning as a physical barricade to stop the entry of pathogens, also hosts innumerable commensal organisms. The skin cells and the immune system constantly interact with microbes, to maintain cutaneous homeostasis, despite the challenges offered by various environmental factors. A major environmental factor affecting the skin is ultraviolet radiation (UV-R) from sunlight. UV-R is well known to modulate the immune system, which can be both beneficial and deleterious. By targeting the cells and molecules within skin, UV-R can trigger the production and release of antimicrobial peptides, affect the innate immune system and ultimately suppress the adaptive cellular immune response. This can contribute to skin carcinogenesis and the promotion of infectious agents such as herpes simplex virus and possibly others. On the other hand, a UV-established immunosuppressive environment may protect against the induction of immunologically mediated skin diseases including some of photodermatoses such as polymorphic light eruption. In this article, we share our perspective about the possibility that UV-induced immune suppression may alter the landscape of the skin's microbiome and its components. Alternatively, or in concert with this, direct UV-induced DNA and membrane damage to the microbiome may result in pathogen associated molecular patterns (PAMPs) that interfere with UV-induced immune suppression.

Pub.: 26 Aug '16, Pinned: 15 Jul '17