Viral Surveillance and Life Cycle Research: The Essential Work Empowering Public Health

Virology research is one particularly vital basic research field, as it studies infectious diseases with the potential to cause mass societal harm. By investigating emerging diseases, surveilling pathogen populations, and studying virus life cycles and characteristics, researchers collect valuable information that helps to predict outbreaks, reduce transmission, and supports the design of vaccines and therapeutics.

Many decades of basic virology research made the design and execution of SARS-CoV-2 intervention strategies faster and more efficient. Look no further than the unprecedented pace of vaccine development that was achieved in response to COVID-19[1]. By studying other coronaviruses (like, SARS and MERS) and other RNA viruses (like, influenza and HIV) researchers primed the scientific community for rapid execution with COVID-19. In effect, this propelled discovery during a time of tremendous need as the world grappled with a “once-in-a-century” pandemic.

This article provides an overview of two key areas of basic virology research—viral surveillance and viral life cycle studies—along with some of the methods researchers use to answer foundational questions, long before emergencies arise.

Viral surveillance[2] is a core pillar of public health research, where scientists analyze animal, human, and/or environmental samples for the presence of both known and unknown viruses. Along with detecting viruses and understanding their epidemiological impact, the programs often track genomic information to understand viral evolution and transmission. This information helps public health organizations stay ahead of emerging viruses and mutations, pre-empting large scale breakouts.

Modern molecular viral surveillance generally begins with genome sequencing, often relying on next-generation sequencing (NGS) approaches due to their increased sensitivity and accuracy. Decoding the genome of a virus in a real-world sample provides researchers with a snapshot of genetic information. By analyzing this snapshot and cross comparing sequences across viral genomic databases, researchers can identify both novel and well-known viruses, detect conserved gene sequences, and closely follow mutations driving viral evolution.

The power of viral surveillance sequencing efforts really shines once many snapshots of a given virus are collected from a variety of geographic areas and assembled into more actionable phylogenetic information. For example, by April of 2021, researchers deposited over 1.2 million SARS-CoV-2 genomic sequences in a repository hosted by the Global Initiative on Sharing Avian Influenza Data (GISAID) [3]. Together, RNA sequencing (RNA-seq) data has helped researchers understand more about COVID-19’s origins[4], track the epidemiology of outbreaks[5], and follow variant emergence and spread[6]. Researchers have also used phylogenetic information to understand the impact of community transmission and superspreader events[7].

While NGS and RNA-seq are vital for capturing a complete picture of viral genomes as they emerge and spread, both methods have limitations. Specifically, it can be difficult to execute genomic sequencing at the scale, speed, and cost needed to closely follow transmission in all patient samples. Furthermore, sequencing still requires access to sophisticated laboratories and instrumentation. This can make it difficult to launch massive sequencing efforts worldwide and in the field.

To complement NGS, viral surveillance teams also leverage other nucleic acid-based technologies to more quickly detect and track viruses at a larger scale, across the globe.

PCR technology became a household term during the COVID-19 pandemic. Indeed, RT-qPCR remains the gold standard for detecting SARS-CoV-2 positive samples.

Though most researchers are probably familiar with how PCR, qPCR, and RT-PCR work, they may be less familiar with up-and-coming nucleic acid detection technologies like isothermal nucleic acid amplification assays. In particular, use of loop-mediated isothermal amplification (LAMP) tests[8] has grown in the COVID-19 era. This approach provides good diagnostic performance with shorter, simplified workflows and applications in point-of-care and at-home testing.

LAMP uses multiple (4-6) primers to amplify target sequences. Importantly, the two “inner” primers create DNA products with sequences on either end that are complementary to internal regions of the product. After hybridization of complementary regions, the product forms what is known as a “dumbbell” structure. This can then be amplified further using the remaining primers to create a variety of DNA products. Once the amplification step is complete, users can adopt a variety of approaches to detect the presence or absence of the target sequence in a variety of ways, including DNA binding dyes. However, more complex approaches have also been adapted to improve sensitivity and specificity, including LAMP workflows using CRISPR systems[9].

Collectively, by pairing both genome sequencing and more accessible nucleic acid techniques, researchers can more closely surveil viral species. The power of this information is further strengthened by additional techniques like serology and immunohistochemistry. However, to take our understanding to the next level, researchers must also investigate viral life cycles and closely characterize their biologic activities.

Characterizing a virus’s life cycle is another critical area of virology research. The primary goal is to understand the various molecular steps a virus takes to produce progeny in a host cell. In doing so, researchers unpack the steps needed for successful viral replication, including critical binding events, vital enzymatic activities, essential host factors, and more. Research teams can then use this information to counter the virus, identifying drug targets, selecting vaccine antigens, determining how mutations alter viral fitness, and beyond.

For example, researchers have used genome wide CRISPR screening to identify host factors central to influenza viral replication[10]. This research identified new potential drug targets for Influenza infections. Researchers also took a similar screening approach for SARS-CoV-2 [10]. As the vast majority of viruses have limited or no anti-viral medicines, these studies offer drug developers new avenues to explore in otherwise limited spaces.

In recent years, viral transcriptomics has emerged as a popular tactic for understanding viral life cycles. Using RNA-seq, researchers can track the totality of RNA transcripts—including both viral and host transcripts—before, during, and after infection. Among many potential applications of this analysis, researchers can use transcriptomics to track the emergence of viral variants and study why clinical presentation of viral illness can differ between hosts[11]. With the growth of improved transcriptomic workflows and superior reverse transcriptases, researchers are also applying these approaches to the single-cell level to capture nuances otherwise lost in bulk cellular analysis.

Now more than ever, the public recognizes the value of ongoing virology research and how it contributes to health and safety. With further adoption and exploration of newer methods, like LAMP and viral transcriptomics, researchers can unlock the complexities of viruses and further mitigate their impacts. It’s part of an ongoing mission to enhance virological tools and improve our response to future outbreaks. To prepare for evolving viral threats, our research tactics also must continually evolve.

Recognizing this need, Thermo Fisher Scientific has placed new emphasis on supporting virology researchers worldwide.

For more information and details on relevant research tools from Thermo Fisher Scientific, check out our Virology Resource Page.

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