Friday, 06 April 2018 17:35

Catching the same disease twice…at the same time

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Published in mBiosphere

Can you catch the same disease twice? Whether you can experience the same disease at different times often depends on immunity generated from the previous infection. Whether you can catch two variants of the same disease at the same time is a different question. A recent Journal of Virology study looks at the ability of two strains of the human papillomavirus (HPV) to coinfect the same cell, finding that specific strains are better at blocking coinfection than others. 

JVirology: Superinfection exclusion between two high-risk human papillomavirus types during a coinfection

The findings are relevant for the estimated 79 million Americans currently infected with HPV, roughly half of whom are infected by more than one strain. Do these different infectious strains have discrete infectious foci or can they coinfect a single cell–a process known as superinfection? First author Jennifer Biryukov with senior scientist Craig Meyers investigated whether two different HPV strains could infect the same cell.

HPV is of particular concern because of its link to cancer. Two HPV strains, HPV16 and HPV18, are particularly associated with oncogenesis, though other strains can also be oncogenic. The researchers examined the relationship between coinfection with HPV16 and HPV18 by comparing the expression rates of viral genes. Their data show that HPV18 infectivity is decreased in the presence of HPV16 during coinfection with both viruses. 

To determine how one virus inhibits the other, the scientists systematically looked at several stages of viral infection. They found that when both viral genomes were transfected inside the same cell, both genomes would be transcribed, ruling out differential transcription rates as the limiting step. The authors then looked at viral attachment. When both viruses were added to cell culture at the same time, HPV16 was internalized at a higher rate than HPV18. These internalization differences were due to variations in the capsid protein L2 sequence, which confers the binding preferences of the strains.

2018.4.6 figure 2Immortalized (A) or primary keratinocytes (B) were incubated with HPV16, HPV18 or both. After 2 h, the number of virus particles attached was quantified via qPCR against a standard curve of known concentrations of HPV genomes. Source.

How is HPV16 internalized into cells more quickly than HPV18? HPV16 and HPV18 have different dependencies on extracellular matrix (ECM) heparin sulfate proteoglycans for infection, which the authors hypothesized may be due to different attachment requirements. Localization studies showed that HPV16 bound more efficiently to cell surfaces, which HPV18 bound more efficiently to the ECM than to the cells themselves. In fact, HPV16 attachment blocked HPV18 attachment in both immortalized and primary cells (see figure, right). This superinfection exclusion was reversed when HPV18 was engineered to express the L2 sequence from HPV16.  

It’s worth noting that these results most likely reflect what would happen if uninfected cells became infected with multiple strains at once. Other data from the study showed that cells maintaining episomal HPV genomes, meaning genomes not expressing the HPV genes or producing progeny virions, were able to be infected by a secondary strain. This suggests that cells may be infected by a second HPV strain if enough time has passed after infection with a first. Interactions between two viral strains may affect the cumulative outcome of cell infection, and thus warrants more in-depth study.

Cover photo source

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Last modified on Wednesday, 11 April 2018 10:45
Julie Wolf

Julie Wolf is the ASM Science Communications Specialist. She contributes to the ASM social media and blog network and hosts the Meet the Microbiologist podcast. She also runs workshops at ASM conferences to help scientists improve their own communication skills. Follow Julie on Twitter for more ASM and microbiology highlights at @JulieMarieWolf.

Julie earned her Ph.D. from the University of Minnesota, focusing on medical mycology and infectious disease. Outside of her work at ASM, she maintains a strong commitment to scientific education and teaches molecular biology at the community biolab, Genspace. She lives in beautiful New York City.

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