Wasps do a gain-of-function experiment in caterpillars

parasitic waspParasitic wasps (in the order Hymenoptera) inject their eggs into lepidopteran hosts, where the eggs go through their developmental stages. Along with the eggs, the wasps also deliver viruses carrying genes encoding proteins that inhibit caterpillar immune defenses. Some of these genes are permanently transferred to the lepidopteran host where they have assumed new defensive functions against other viruses.

The viruses that parasitic wasps inject with their eggs, called Bracoviruses, are encoded in the wasp genome. About 100 million years ago a nudivirus genome integrated into the genome of a common wasp ancestor. With time the viral genes became dispersed in the wasp genome. The viruses produced by these wasps today no longer carry capsid coding genes – they are found only in the wasp genome – but only carry genes whose products can modulate lepidopteran defenses. Once in the lepidopteran host, these viruses deliver their genes but no longer form new particles.

An important question is whether wasp Bracoviruses can contribute genes to Lepidoptera – a process called horizontal gene transfer. This possibility would seem remote because the lepidopteran hosts for wasp larvae are dead ends – they die after serving as hosts for wasp development. However, it is possible that some hosts resist killing, or that wasps occasionally inject their eggs and viruses into the wrong host, one that can resist killing.

To answer this question, the genome sequence of Cotesia congregata bracovirus was compared with the genomes of a regular host as well as non-host Lepidoptera. Bracovirus DNA insertions were identified in genomes of the monarch, the silkworm, the beet armyworm and the fall armyworm, but not in the genome of the tobacco hornworm, the usual host of the wasp (C. congregata).

Not only were the Bracovirus sequences found in these varied Lepidoptera, but some appeared to be functional. Two such genes encode a protein that interferes with the replication of baculovirus, a known pathogen of Lepidoptera. This discovery was made in the process of producing the encoded proteins using baculovirus vectors! In other words, viral genes delivered by Hymenopteran wasps were appropriated by the Lepidoptera and used for their defense against a pathogen.

To put it another way, nature has carried out a gain-of-function experiment. Should we impose a moratorium?

The delivery of immunosuppressive viruses by wasps along with their eggs is by all accounts a remarkable story. The appropriation of some of these genes by the wrong hosts should not come as a surprise, yet the finding is nevertheless simply amazing. As long as we keep looking, we will find that the biological world is always full of new revelations.

TWiV 355: Baby’s first virome

On episode #355 of the science show This Week in Virology, the TWiV team considers the effect of a Leishmaniavirus on the efficacy of drug treatment, and the human fecal virome and microbiome in twins during early infancy.

You can find TWiV #355 at www.microbe.tv/twiv.

A virus in a parasite in a human

Cutaneous leishmaniaThe protozoan parasite Leishmania, transmitted to humans by the bite of a sandfly, may cause disfiguring skin lesions. A virus within the parasite appears to increase the risk of treatment failure with anti-leishmania drugs.

A double-stranded RNA virus was found over 20 years ago to infect different species of Leishmania, with up to 50% of clinical isolates infected. Leishmaniavirus (LRV) causes a chronic infection with little effect on the parasite. In mouse models, infection of Leishmania with LRV is associated with increased parasite replication and disease severity. The double-stranded RNA genome of LRV appears to be sensed by the mammalian innate immune system, leading to overproduction of cytokines and a hyper-inflammatory response. Similarly, the dsRNA of Trichomonas vaginalis virus is also sensed by the innate immune system, leading to inflammatory complications.

Two independent studies have been done to assess the consequence of LRV infection in human cases of leishmaniasis. In one study, presence of LRV was determined in Leishmania braziliensis isolated from 97 patients in Peru and Bolivia. The patients were treated with pentavalent antimonials or amphotericin B, and the outcome was determined as ‘cured’ or ‘failure’. Thirty-two (33%) Leishmania isolates were found to contain LRV.   Treatment failed in 33% of the patients (18 of 54). There were fewer drug failures in the LRV negative isolates (9 of 37, 24%) than in the LRV positive isolates 9 of 17, 53%). These observations demonstrate that presence of LRV is associated with a significant increase in the risk of treatment failure.

In the second study, carried out in French Guiyana, 58% of 75 patients with Leishmania guyanensis infection had LRV in the parasite. All the patients with LRV-negative Leishmania were cured after one or two treatments with pentamidine, while 12 of 44 LRV-positive patients (27%) had persistent infections requiring treatment with other drugs. In addition, presence of LRV was associated with high levels of inflammatory cytokines within lesions.

The results of both studies show that infection of Leishmania with LRV is associated with drug treatment failure and persistent infection. Determining whether LRV is present in infected patients could therefore guide better treatment strategies. How the presence of the virus leads to such consequences is unknown. The effect might be a consequence of higher parasite numbers associated with LRV infection, which simply overcome already marginal drugs. The host inflammatory response caused by the dsRNA of LRV might also play a role. Understanding the precise mechanism might allow the development of drugs that overcome the effects of LRV. It might also be useful to develop drugs that target LRV, thereby improving the efficacy of anti-Leishmania drugs.

TWiP 41: Flying and crawling beasts

On episode #41 of the science show This Week in Parasitism, Vincent and Dickson review medically important arthropods.

You can find TWiP #41 at microbeworld.org/twip.

TWiP 38: How to Trichomonas

On episode #38 of the science show This Week in Parasitism, Vincent and Dickson tackle the backlog of listener email, then consider the life cycle and pathogenesis of Trichomonas vaginalis, the flagellated protozoan transmitted by sexual contact.

You can find TWiP #38 at microbeworld.org/twip.

TWiP 32: Evasive trypanosomes and schistosomes

t cruzi and  nfkbHosts: Vincent Racaniello and Dickson Despommier

Vincent and Dickson discuss immune evasion by the cruzain protease of T. cruzi, and novel tetraspanin antigens of S. japonicum.

Click the arrow above to play, or right-click to download TWiP #32 (65 MB .mp3, 90 minutes).

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TWiP 31: A malaria vaccine

p.falciparum life cycleHosts: Vincent Racaniello and Dickson Despommier

Vincent and Dickson discuss the promising results of a phase III trial of a malaria vaccine in African children.

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TWiP 30: Global infectious disease control with Charles Knirsch

Charles KnirschHosts: Vincent Racaniello and Dickson Despommier

Vincent and Dickson have a broad-ranging conversation with Charles Knirsch of Pfizer, Inc. about how public-private partnerships can function to control and eliminate infectious diseases.

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TWiP 29: Neglected tropical diseases with Peter Hotez

hotez and clintonHosts: Vincent Racaniello and Dickson Despommier

Vincent and Dickson converse with Peter Hotez about global health, vaccinology, and neglected tropical diseases.

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TWiP 28: Medical entomology with Robert W. Gwadz

anopheles gambiaeHosts: Vincent Racaniello and Dickson Despommier

On episode #28 of the podcast This Week in Parasitism, Vincent and Dickson discuss medical entomology with Robert W. Gwadz, Assistant Chief of the Laboratory of Malaria and Vector Research at NIAID.

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TWiP #28 (65 MB .mp3, 91 minutes)