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Comment by virusduck | Hacker News Reader

This is not surprising. At least one study [1] showed 85% of people's brains are PCR-positive for at least HHV-6. It is also important to keep in mind that herpesviruses have evolved with us (and many other species) and in some ways are considered part of our normal flora. They may also play an important role in the proper development of our immune system.

The data in this paper is suggestive (and complicated!!), but there is no convincing mechanism for the virus having anything to do with the development of Alzheimers. The real virology here will be very hard.

[1] https://www.ncbi.nlm.nih.gov/pubmed/11285567

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Likewise, detectable RNA/DNA does not mean there's virus (virions).

An unusual example, but it's common to have Ebola virus RNA in semen (a fluid from another immuno-privileged site) with no detectable virus for months after primary infection. (https://www.nejm.org/doi/full/10.1056/nejmoa1511410 among others.) Similar patterns exist for lots of other viruses.

True, but keep in mind:

It is a normal part of all herpesviruses to be quiescent. They have the capacity to reactivate from nothing but their genome into a fully functional virus.

Ebola is a negative-stranded RNA virus, and it is unlikely to find naked RNA in any body site. Rather, it is a mix of infectious virions and noninfectioius virus-like particles. The NEJM study you site was a qRTPCR only study. There was no attempt to actually culture the virus from the semen. Previous studies have tried culturing, and it difficult to culture semen-derived virus at the qRTPCR titers identified here.

So why don't they try to isolate the virus itself instead of looking for RNA/DNA? Too expensive? Or impossible perhaps?

This is more difficult than is sounds. Herpesviruses are quiescent (latent) for much of their lives and exist only as DNA, with no virions being produced. There are different latency "programs"--during some of these, there may be a handful of virus genes produced, and some there are no genes produced. Circumstances may cause these virus genomes to reactivate--transcribing genes and making virions.

Maybe confusingly, herpesviruses may still contribute to the biology of the cell even in the latent state.

DNA/RNA sequencing is also more sensitive in some ways (which can be both good and bad). It is also a very broad tool. You can go back to large datasets and try to squeeze more information out--even things you werent looking for originally, like herpesviruses. NCBI also hosts a very large repository of raw sequence data (SRA--the sequence read archive). Much of this data has decent metadata, so you could conceivably even do a new study on somebody else's old data.

Realistically, probably because they're not virologists. Looking for nucleic acids is easy/commonplace. Virus culture, electron microscopy and immunoassays are more specialized techniques.

If they aren't virologists, maybe they should leave this kind of research to those that are? The headline says "Researchers Find Herpes Viruses" ...but they didn't (or cannot?) find them? Then, umm...why does it say that?

People commonly take acyclovir for simplex 1 & 2. Does that suppress this virus? Can any of these common drugs pass the blood-brain barrier?

Might other herpes strains be involved? Zoster (chicken pox)? Epstein-Barr (mono)? Kaposi's Sarcoma/HHV8?

Acyclovir improves outcomes in HSV encephalitis [0], but does not completely cure it or prevent long-term damage in all patients.

The worst side effect of encephalitis is memory impairment:

> The most common and most disabling complication of herpes simplex encephalitis in our patients, and in other studies,9 10 20-24 was memory impairment, which especially affected short term memory. Occasionally remote memory is more severely affected than anterograde memory.

[0] https://jnnp.bmj.com/content/63/3/321

Don't forget Cytomegalovirus (CMV, or HHV-5)! (Also, the zoster/chickenpox virus is calle Varicella-zoster virus (VZV or HHV-3).

Since there is no proposed mechanism for how the virus may be involved, there is no way to know if acyclovir, cidofovir, or any nucleoside analog might help. These drugs only really help to stop actively replicating viruses (lytic viruses). Most of the herpesvirus life cycle is spent in "latency" where it only exists as a piece of DNA (some, like HHV6/7 may integrate into the host chromosome, others like HSV-1/HHV-1 and EBV/HHV-4 maintain their genome as a separate molecule). During this period, there are few, if any, genes made, but in some cases, those genes may be important to disease pathogenesis. The role of herpesviruses in latency-associated diseases is very complicated, and is also dependent on host genetics.

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