Blocking Zika virus vertical transmission.

The outbreak of the Zika virus (ZIKV) has been associated with increased incidence of congenital malformations. Although recent efforts have focused on vaccine development, treatments for infected individuals are needed urgently. Sofosbuvir (SOF), an FDA-approved nucleotide analog inhibitor of the Hepatitis C (HCV) RNA-dependent RNA polymerase (RdRp) was recently shown to be protective against ZIKV both in vitro and in vivo. Here, we show that SOF protected human neural progenitor cells (NPC) and 3D neurospheres from ZIKV infection-mediated cell death and importantly restored the antiviral immune response in NPCs. In vivo, SOF treatment post-infection (p.i.) decreased viral burden in an immunodeficient mouse model. Finally, we show for the first time that acute SOF treatment of pregnant dams p.i. was well-tolerated and prevented vertical transmission of the virus to the fetus. Taken together, our data confirmed SOF-mediated sparing of human neural cell types from ZIKV-mediated cell death in vitro and reduced viral burden in vivo in animal models of chronic infection and vertical transmission, strengthening the growing body of evidence for SOF anti-ZIKV activity

Elucidation of the transmission patterns of an insect-borne bacterium

Quantitative data on modes of transmission are a crucial element in understanding the ecology of microorganisms associated with animals. We investigated the transmission patterns of a -proteobacterium informally known as pea aphid Bemisia-like symbiont (PABS), also known as T-type, which is widely but not universally distributed in natural populations of the pea aphid, Acyrthosiphon pisum. The vertical transmission of PABS to asexual and sexual morphs and sexually produced eggs was demonstrated by a diagnostic PCR-based assay, and the maximum estimated failure rate was 2%. Aphids naturally lacking PABS acquired PABS bacteria administered via the diet, and the infection persisted by vertical transmission for at least three aphid generations. PABS was also detected in two of five aphid honeydew samples tested and in all five siphuncular fluid samples tested but in none of 15 samples of salivary secretions from PABS-positive aphids. However, PABSnegative aphids did not acquire PABS when they were cocultured with PABS-positive aphids; the maximal estimated level of horizontal transmission was 18%. A deterministic model indicated that the force of infection by a horizontal transmission rate of 3% is sufficient to maintain a previously described estimate of the prevalence of PABS-positive aphids (37%), if the vertical transmission rate is 98%. We concluded that PABS infections in A. pisum can be maintained by high vertical transmission rates and occasional horizontal transmission, possibly via the oral route, in the absence of selection either for or against aphids bearing this bacterium

Symbiosis through exploitation and the merger of lineages in evolution

A model for the coevolution of two species in facultative symbiosis is used to investigate conditions under which species merge to form a single reproductive unit. Two traits evolve in each species, the first affecting loss of resources from an individual to its partner, and the second affecting vertical transmission of the symbiosis from one generation to the next. Initial conditions are set so that the symbiosis involves exploitation of one partner by the other and vertical transmission is very rare. It is shown that, even in the face of continuing exploitation, a stable symbiotic unit can evolve with maximum vertical transmission of the partners. Such evolution requires that eventually deaths should exceed births for both species in the free-living state, a condition which can be met if the victim, in the course of developing its defences, builds up sufficiently large costs in the free-living state. This result expands the set of initial conditions from which separate lineages can be expected to merge into symbiotic units

Evaluation of the epidemiological importance of classical swine fever infected, E2 sub-unit marker vaccinated animals with RT-nPCR positive blood samples

&lt;p&gt;It has been demonstrated that pigs that have been double vaccinated with an E2 sub-unit marker vaccine and that are infected with classical swine fever virus (CSFV) through a natural contact infection may react positive in a CSFV detecting RT-nPCR test, whereas no virus could be isolated by using the conventional virus isolation (VI) technique. To evaluate whether these vaccinated and infected pigs may spread the virus, three experiments were set up. In the first, susceptible pigs were inoculated with serum originating from vaccinated RT-nPCR positive pigs. In the second, vaccinated RT-nPCR positive pigs were brought into contact with sentinel animals. In the third, vertical transmission was evaluated in RT-nPCR positive vaccinated pregnant gilts. In the first two experiments, no proof of virus transmission was found, whereas in the third vertical transmission was observed. The conclusion is that in vaccinated pigs that are positive in RT-nPCR but negative in VI, the level of circulating virus is probably not high enough for horizontal transmission, whereas vertical transmission of the virus is possible.&lt;/p&gt;</p

Evidence for high levels of vertical transmission in Toxoplasma gondii

Toxoplasma gondii is a highly ubiquitous and prevalent parasite. Despite the cat being the only definitive host, it is found in almost all geographical areas and warm blooded animals. Three routes of transmission are recognised: ingestion of oocysts shed by the cat, carnivory and congenital transmission. In natural populations, it is difficult to establish the relative importance of these routes. This paper reviews recent work in our laboratory which suggests that congenital transmission may be much more important than previously thought. Using PCR detection of the parasite, studies in sheep show that congenital transmission may occur in as many as 66% of pregnancies. Furthermore, in families of sheep on the same farm, exposed to the same sources of oocysts, significant divergent prevalences of Toxoplasma infection and abortion are found between different families. The data suggest that breeding from infected ewes increases the risk of subsequent abortion and infection in lambs. Congenital transmission rates in a natural population of mice were found to be 75%. Interestingly, congenital transmission rates in humans were measured at 19.8%. The results presented in these studies differ from those of other published studies and suggest that vertical transmission may be much more important than previously thought

A Combination of Two Human Monoclonal Antibodies Limits Fetal Damage by Zika Virus in Macaques

Human infection by Zika virus (ZIKV) during pregnancy can lead to vertical transmission and fetal aberrations, including microcephaly. Prophylactic administration of antibodies can diminish or prevent ZIKV infection in animal models, but whether passive immunization can protect nonhuman primates and their fetuses during pregnancy has not been determined. Z004 and Z021 are neutralizing monoclonal antibodies to domain III of the envelope (EDIII) of ZIKV. Together the two antibodies protect nonpregnant macaques against infection even after Fc modifications to prevent antibody-dependent enhancement in vitro (ADE) and extend their half-lives. Here we report on prophylactic co-administration of the Fc-modified antibodies to pregnant rhesus macaques challenged 3 times with ZIKV during first and second trimester. The two antibodies did not entirely eliminate maternal viremia but limited vertical transmission protecting the fetus from neurologic damage. Thus, maternal passive immunization with two antibodies to EDIII can shield primate fetuses from the harmful effects of ZIKV

VERTICAL TRANSMISSION OF CONSUMPTION BEHAVIOR AND THE DISTRIBUTION OF SURNAMES

This paper attempts to detect the existence of links in consumptionpreferences between generations. Preferences for consumption goods may bedetermined by the preferences of parents (vertical transmission) and/or bypreferences arising from the environment (horizontal transmission). Wepropose an indirect methodology to overcome the lack of data on consumptionchoices of dynasties, i.e., parents and their adult offspring. This new approachis based on the analysis of the correlation between the geographicaldistributions of surnames and consumption choices. Our results show that thereis horizontal transmission of preferences regarding non-food items and possiblyvertical transmission for food items.Preference formation, surnames, vertical and horizontal transmission.