Viruses & Us: Good, Bad, and Complex

Viruses, which are microscopic, non‑cellular agents that hijack living cells, can be both lethal foes and unexpected allies. In this piece, we explore two very different viruses: HIV, a persistent human pathogen, and CTXφ, a bacteriophage that transforms a harmless bacterium into a deadly one. Each of these cases reveals surprising lessons about biology and medical innovation.

HIV: Human Immunodeficiency Virus

What is HIV and how does it work? HIV is a retrovirus that attacks the immune system by targeting CD4⁺ helper T cells . It uses the enzyme reverse transcriptase to convert its RNA into proviral DNA, which is then integrated into the host genome. That integrated DNA can remain active or lie dormant, making HIV a lifelong infection without treatment. Over time, the gradual loss of CD4⁺ T cells causes Acquired Immunodeficiency Syndrome (AIDS), leading to fatal opportunistic infections if left unchecked.

Treatment & The Quest for a Cure

Modern antiretroviral therapy (ART) reduces viral load, thus preventing disease progression, but it cannot eliminate latent reservoirs. For decades, scientists have been hunting for actual cures. In 2008, the "Berlin Patient" received a stem-cell transplant from a donor with a CCR5-Δ32 mutation, a naturally occurring genetic variant that blocks HIV entry as it lacks the CCR5 coreceptor that HIV binds to. Remarkably, the patient has remained HIV-free ever since. Then, in 2019, Adam Castillejo, better known as the "London Patient", underwent a similar procedure and also achieved sustained remission.

Most recently, a man from Germany, famously known as the "Düsseldorf Patient", became the third individual cured of HIV following a stem cell transplant with CCR5-Δ32 donor cells. By 2023, five patients in total have shown no detectable expression of HIV after undergoing this treatment, a milestone that shifted the “cure” from theoretical to proven in select cases.

But stem cell transplants come with high risks, like graft-versus-host disease, and aren't a scalable cure. Researchers are pivoting toward less invasive options, such as:

• Gene therapy: editing a patient’s own hematopoietic stem cells to mimic CCR5-Δ32 mutations, which potentially grants HIV resistance without donor tissue.

• Immunotherapies: using engineered immune cells (CAR-T cells) or antibody treatments to find and purge HIV reservoirs.

• Latency-reversing agents: "shock and kill" strategies aim to wake up dormant viruses, hence making infected cells visible to the immune system.

Even though we’ve progressed from managing HIV infections to curing them in a select few cases, the ethical dilemma remains: how do we make these risky procedures available to those in greatest need, globally and equitably?

Introducing: Bacteriophages

Bacteriophages are commonly seen as our microbial saviours. They are viruses that infect bacteria. In a post‑antibiotic age, they’re attracting attention as natural bacterial killers. Unlike broad-spectrum antibiotics, phages are host-specific and can evolve alongside their bacterial targets, hence reducing resistance. This has led many scientists to view phages as potential allies in medicine and environmental hygiene.

CTXφ: A Bacteriophage That Turbocharges its Host

However, CTXφ defies that stereotype. It infects Vibrio cholerae, the bacterium behind cholera. Rather than killing it, though, CTXφ integrates into its genome through a process called lysogeny. The result? The benign bacterium now produces cholera toxin, turning harmless environmental strains into virulent pathogens. CTXφ’s approximately 7 kb genome includes the cholera toxin genes (ctxA and ctxB) plus genes essential for replication, regulation, and secretion (e.g., rstR, cep, ace, zot). The phage uses two bacterial structures, the toxin-coregulated pilus (TCP) and the TolQRA complex, for integration and replication. This lysogenic conversion is biologically remarkable but troubling for humans. Without CTXφ, V. cholerae remains harmless and non-toxic.

Public Health & Evolution

Lysogenic phages like CTXφ are major drivers of bacterial evolution and disease emergence. Since CTXφ can transfer its genes horizontally between V. cholerae strains, and even package itself to infect others, it spreads virulently. Environmental conditions, such as sunlight, can induce the phage's release, turning dormant reservoirs into active threats.

Furthermore, phage interactions, like cooperation with other filamentous phages (eg. TLCφ), enable CTXφ to integrate into bacterial chromosomes, hence deepening its hold. In nature, V. cholerae strains lacking toxin genes co-exist, but acquisition of CTXφ can convert them into pandemic-causing agents. Studying CTXφ reveals how viruses shape bacterial ecology, evolution, and pathogenesis.

Lessons for a Biology Student 🧑‍🎓

While wildly differing in origin and mechanism of infection, both HIV & CTXφ share common themes of inserting their own genome into that of their hosts, remaining latent in reservoirs, posing a looming threat to public health, & resisting eradication. The popular idea of phages as guardian angels that can protect us from bacteria is also oversimplified. CTXφ shows that a phage can be a toxin supplier, not necessarily a bacterial assassin.

The Future: Innovation, Caution, & Equity

Gene-editing therapies show promise for curing HIV, but they must be safe, accessible, affordable, and scalable. The Düsseldorf and other CCR5 cases prove it's possible, but costly and high-risk. Ethics demand that the journey to the cure must avoid widening inequalities.

As for phages, designed phage therapies targeting antibiotic-resistant bacteria are gaining traction, but the case of CTXφ warns us against neglecting the mechanisms of viral gene transfer and unintended consequences. Ethical phage deployment requires environmental genomic surveillance and transparency.

Conclusion

From HIV to CTXφ, viruses remind us that microscopic agents have outsized effects on human health. HIV’s integration into human cells taught us about the power, and limitations, of antiviral approaches. On the other hand, CTXφ teaches us we cannot assume all phages are beneficial; their genomic integration may drive epidemics like cholera.

As biology students, understanding these viral strategies is vital, not just for biology, but for grappling with medical advances and moral responsibilities. In an age of gene editing, phage therapy, and viral pandemics, we must be intellectually equipped, ethically grounded, and scientifically vigilant.

References

1. Pardo E. (2023, May 20). Germany’s “Düsseldorf patient” cured of HIV – DW – 02/20/2023. https://www.dw.com/en/germanys-d%C3%BCsseldorf-patient-cured-of-hiv/a-64766961

2. Faruque SM, Asadulghani, et al. (1998, August). Induction of the lysogenic phage encoding cholera toxin in naturally occurring strains of toxigenic vibrio cholerae O1 and O139. Infection and immunity. https://pmc.ncbi.nlm.nih.gov/articles/PMC108411/

3. Fan F & Kan B. (2015, January 20). Survival and proliferation of the lysogenic bacteriophage CTXΦ in vibrio cholerae - virologica sinica. SpringerLink. https://link.springer.com/article/10.1007/s12250-014-3550-7

4. Hassan F, Kamruzzaman M, et al. (2010, October 13). Satellite phage tlcφ enables toxigenic conversion by CTX phage through DIF site alteration. Nature News. https://www.nature.com/articles/nature09469

5. Pant A, Das B, et al. (2019, July 1). Ctx phage of vibrio cholerae: Genomics and applications. CTX phage of Vibrio cholerae: Genomics and applications. https://www.sciencedirect.com/science/article/pii/S0264410X19307960

Image Credit

1. https://www.aidsmap.com/about-hiv/hiv-lifecycle