Hepatitis B testing, treatment, and virologic suppression in HIV-infected patients in Cameroon (ANRS 12288 EVOLCAM).

BACKGROUND: Hepatitis B is a major concern in Africa, especially in HIV-infected patients. Unfortunately, access to hepatitis B virus (HBV) testing and adequate treatment remains a challenge in the continent. We investigated HBV testing, treatment, and virologic suppression in HIV-infected patients followed up as part of Cameroon's national antiretroviral programme. METHODS: A cross-sectional survey was performed in adult patients receiving antiretroviral therapy (ART) in 19 hospitals in the Centre and Littoral regions in Cameroon. The proportions of patients tested for hepatitis B surface antigen (HBsAg) prior to the study were compared among all study hospitals using the Chi-square test. The association of individual and hospital-related characteristics with HBV testing and virologic suppression was assessed using multilevel logistic regression models. RESULTS: Of 1706 patients (women 74%, median age 42 years, median time on ART 3.9 years), 302 (17.7%) had been tested for HBsAg prior to the study. The proportion of HBV-tested patients ranged from 0.8 to 72.5% according to the individual hospital (p < 0.001). HBV testing was lower in women (adjusted odds ratio [aOR] 0.64, 95% confidence interval [CI] 0.46-0.89, p = 0.010) and higher in patients who initiated ART in 2010 or later (aOR 1.66, 95% CI 1.23-2.27, p < 0.001). Of 159 HBsAg-positive patients at the time of the study (9.3%), only 97 (61.0%) received Tenofovir + Lamivudine (or Emtricitabine). Of 157 coinfected patients, 114 (72.6%) had a HBV viral load < 10 IU/mL. HBV suppression was higher in patients with a HIV viral load < 300 copies/mL (aOR 3.46, 95% CI 1.48-8.09, p = 0.004) and lower in patients with increased ALT level (aOR 0.86 per 10 IU/mL increase, 95% CI 0.75-0.97, p = 0.019). CONCLUSIONS: A substantial proportion of HIV/HBV coinfected patients were at higher risk of liver disease progression. Improving the management of HBV infection in the routine healthcare setting in Africa is urgently required in order to achieve the 2030 elimination targets. Micro-elimination of HBV infection in people living with HIV could be an easier and cost-effective component than more widely scaling up HBV policies.

SAMHD1 Enhances Chikungunya and Zika Virus Replication in Human Skin Fibroblasts.

Chikungunya virus (CHIKV) and Zika virus (ZIKV) are emerging arboviruses that pose a worldwide threat to human health. Currently, neither vaccine nor antiviral treatment to control their infections is available. As the skin is a major viral entry site for arboviruses in the human host, we determined the global proteomic profile of CHIKV and ZIKV infections in human skin fibroblasts using Stable Isotope Labelling by Amino acids in Cell culture (SILAC)-based mass-spectrometry analysis. We show that the expression of the interferon-stimulated proteins MX1, IFIT1, IFIT3 and ISG15, as well as expression of defense response proteins DDX58, STAT1, OAS3, EIF2AK2 and SAMHD1 was significantly up-regulated in these cells upon infection with either virus. Exogenous expression of IFITs proteins markedly inhibited CHIKV and ZIKV replication which, accordingly, was restored following the abrogation of IFIT1 or IFIT3. Overexpression of SAMHD1 in cutaneous cells, or pretreatment of cells with the virus-like particles containing SAMHD1 restriction factor Vpx, resulted in a strong increase or inhibition, respectively, of both CHIKV and ZIKV replication. Moreover, silencing of SAMHD1 by specific SAMHD1-siRNA resulted in a marked decrease of viral RNA levels. Together, these results suggest that IFITs are involved in the restriction of replication of CHIKV and ZIKV and provide, as yet unreported, evidence for a proviral role of SAMHD1 in arbovirus infection of human skin cells.

Phyloepidemiological Analysis Reveals that Viral Divergence Led to the Paucity of Simian Immunodeficiency Virus SIVmus/gsn/mon Infections in Wild Populations.

Human immunodeficiency virus type 1 (HIV-1) is the result of cross-species transmission of simian immunodeficiency virus from chimpanzees (SIVcpz). SIVcpz is a chimeric virus which shares common ancestors with viruses infecting red-capped mangabeys and a subset of guenon species. The epidemiology of SIV infection in hominoids is characterized by low prevalences and an uneven geographic distribution. Surveys in Cameroon indicated that two closely related members of the guenon species subset, mustached guenons and greater spot-nosed guenons, infected with SIVmus and SIVgsn, respectively, also have low rates of SIV infections in their populations. Compared to that for other monkeys, including red-capped mangabeys and closely related guenon species, such an epidemiology is unusual. By intensifying sampling of geographically distinct populations of mustached and greater spot-nosed guenons in Gabon and including large sample sets of mona guenons from Cameroon, we add strong support to the hypothesis that the paucity of SIV infections in wild populations is a general feature of this monophyletic group of viruses. Furthermore, comparative phylogenetic analysis reveals that this phenotype is a feature of this group of viruses infecting phylogenetically disparate hosts, suggesting that this epidemiological phenotype results from infection with these HIV-1-related viruses rather than from a common host factor. Thus, these HIV-1-related viruses, i.e., SIVcpz and the guenon viruses which share an ancestor with part of the SIVcpz genome, have an epidemiology distinct from that found for SIVs in other African primate species.IMPORTANCE Stable virus-host relationships are established over multiple generations. The prevalence of viral infections in any given host is determined by various factors. Stable virus-host relationships of viruses that are able to cause persistent infections and exist with high incidences of infection are generally characterized by a lack of morbidity prior to host reproduction. Such is the case for cytomegalovirus (CMV) and Epstein-Barr virus (EBV) infections of humans. SIV infections of most African primate species also satisfy these criteria, with these infections found at a high prevalence and with rare cases of clinical disease. In contrast, SIVcpz, the ancestor of HIV-1, has a different epidemiology, and it has been reported that infected animals suffer from an AIDS-like disease in the wild. Here we conclusively demonstrate that viruses which are closely related to SIVcpz and infect a subset of guenon monkeys show an epidemiology resembling that of SIVcpz.

Origin of the HIV-1 group O epidemic in western lowland gorillas.

HIV-1, the cause of AIDS, is composed of four phylogenetic lineages, groups M, N, O, and P, each of which resulted from an independent cross-species transmission event of simian immunodeficiency viruses (SIVs) infecting African apes. Although groups M and N have been traced to geographically distinct chimpanzee communities in southern Cameroon, the reservoirs of groups O and P remain unknown. Here, we screened fecal samples from western lowland (n = 2,611), eastern lowland (n = 103), and mountain (n = 218) gorillas for gorilla SIV (SIVgor) antibodies and nucleic acids. Despite testing wild troops throughout southern Cameroon (n = 14), northern Gabon (n = 16), the Democratic Republic of Congo (n = 2), and Uganda (n = 1), SIVgor was identified at only four sites in southern Cameroon, with prevalences ranging from 0.8-22%. Amplification of partial and full-length SIVgor sequences revealed extensive genetic diversity, but all SIVgor strains were derived from a single lineage within the chimpanzee SIV (SIVcpz) radiation. Two fully sequenced gorilla viruses from southwestern Cameroon were very closely related to, and likely represent the source population of, HIV-1 group P. Most of the genome of a third SIVgor strain, from central Cameroon, was very closely related to HIV-1 group O, again pointing to gorillas as the immediate source. Functional analyses identified the cytidine deaminase APOBEC3G as a barrier for chimpanzee-to-gorilla, but not gorilla-to-human, virus transmission. These data indicate that HIV-1 group O, which spreads epidemically in west central Africa and is estimated to have infected around 100,000 people, originated by cross-species transmission from western lowland gorillas.

Differentiation of Staphylococcus argenteus (formerly: Staphylococcus aureus clonal complex 75) by mass spectrometry from S. aureus using the first strain isolated from a wild African great ape.

The species Staphylococcus argenteus was separated recently from Staphylococcus aureus (Tong S.Y., F. Schaumburg, M.J. Ellington, J. Corander, B. Pichon, F. Leendertz, S.D. Bentley, J. Parkhill, D.C. Holt, G. Peters, and P.M. Giffard, 2015). The objective of this work was to characterise the genome of a non-human S. argenteus strain, which had been isolated from the faeces of a wild-living western lowland gorilla in Gabon, and analyse the spectrum of this species in matrix-assisted laser desorption ionization-time of flight mass spectrometry (MALDI-TOF MS). The full genome sequence revealed a scarcity of virulence genes and absence of resistance genes, indicating a decreased virulence potential compared to S. aureus and the human methicillin-resistant S. argenteus isolate MSHR1132T. Spectra obtained by MALDI-TOF MS and the analysis of available sequences in the genome databases identified several MALDI-TOF MS signals that clearly differentiate S. argenteus, the closely related Staphylococcus schweitzeri and S. aureus. In conclusion, in the absence of biochemical tests that identify the three species, mass spectrometry should be employed as method of choice.

Diversity of malaria parasites in great apes in Gabon.

BACKGROUND: Until 2009, the Laverania subgenus counted only two representatives: Plasmodium falciparum and Plasmodium reichenowi. The recent development of non-invasive methods allowed re-exploration of plasmodial diversity in African apes. Although a large number of great ape populations have now been studied regarding Plasmodium infections in Africa, there are still vast areas of their distribution that remained unexplored. Gabon constitutes an important part of the range of western central African great ape subspecies (Pan troglodytes troglodytes and Gorilla gorilla gorilla), but has not been studied so far. In the present study, the diversity of Plasmodium species circulating in great apes in Gabon was analysed. METHODS: The analysis of 1,261 faecal samples from 791 chimpanzees and 470 gorillas collected from 24 sites all over Gabon was performed. Plasmodium infections were characterized by amplification and sequencing of a portion of the Plasmodium cytochrome b gene. RESULTS: The analysis of the 1,261 samples revealed that at least six Plasmodium species circulate in great apes in Gabon (Plasmodium praefalciparum, Plasmodium gorA (syn Plasmodium adleri), Plasmodium gorB (syn Plasmodium blacklocki) in gorillas and Plasmodium gaboni, P. reichenowi and Plasmodium billcollinsi in chimpanzees). No new phylogenetic lineages were discovered. The average infection rate was 21.3% for gorillas and 15.4% for chimpanzees. A logistic regression showed that the probability of infection was significantly dependent on the freshness of the droppings but not of the host species or of the average pluviometry of the months of collection.

Loss of memory CD4+ T-cells in semi-wild mandrills (Mandrillus sphinx) naturally infected with species-specific simian immunodeficiency virus SIVmnd-1.

Simian immunodeficiency virus (SIV) infection is found in a number of African primate species and is thought to be generally non-pathogenic. However, studies of wild primates are limited to two species, with SIV infection appearing to have a considerably different outcome in each. Further examination of SIV-infected primates exposed to their natural environment is therefore warranted. We performed a large cross-sectional study of a cohort of semi-wild mandrills with naturally occurring SIV infection, including 39 SIV-negative and 33 species-specific SIVmnd-1-infected animals. This study was distinguished from previous reports by considerably greater sample size, examination of exclusively naturally infected animals in semi-wild conditions and consideration of simian T-lymphotropic virus (STLV) status in addition to SIVmnd-1 infection. We found that SIVmnd-1 infection was associated with a significant and progressive loss of memory CD4(+) T-cells. Limited but significant increases in markers of immune activation in the T-cell populations, significant increases in plasma neopterin and changes to B-cell subsets were also observed in SIV-infected animals. However, no increase in plasma soluble CD14 was observed. Histological examination of peripheral lymph nodes suggested that SIVmnd-1 infection was not associated with a significant disruption of the lymph node architecture. Whilst this species has evolved numerous strategies to resist the development of AIDS, significant effects of SIV infection could be observed when examined in a natural environment. STLVmnd-1 infection also had significant effects on some markers relevant to understanding SIV infection and thus should be considered in studies of SIV infection of African primates where present.

Significant impact of non-B HIV-1 variants genetic diversity in Gabon on plasma HIV-1 RNA quantitation.

Evaluations of HIV-1 RNA viral load assays are lacking in Central Africa. The main objective of our study was to assess the reliability of HIV-1 RNA results obtained with three different assays for samples collected in Gabon. A total of 137 plasma specimens were assessed for HIV-1 RNA using the Abbott RealTime HIV-1® and Nuclisens HIV-1 EasyQ® version 2.0 assays. It included HIV-1 non-B samples (n = 113) representing six subtypes, 10 CRFs and 18 URFs from patients infected with HIV-1 and treated with antiretrovirals that were found HIV-1 RNA positive (≥300 copies/ml) with the Generic HIV viral load® assay; and samples (n = 24) from untreated individuals infected with HIV-1 but showing undetectable (<300 copies/ml) results with the Biocentric kit. For samples found positive with the Generic HIV viral load® test, correlation coefficients obtained between the three techniques were relatively low (R = 0.65 between Generic HIV viral load® and Abbott RealTime HIV-1®, 0.50 between Generic HIV viral load® and Nuclisens HIV-1 EasyQ®, and 0.66 between Abbott RealTime HIV-1® and Nuclisens HIV-1 EasyQ®). Discrepancies by at least one log10 were obtained for 19.6%, 33.7%, and 20% of samples, respectively, irrespective of genotype. Most of samples (22/24) from untreated study patients, found negative with the Biocentric kit, were also found negative with the two other techniques. In Central Africa, HIV-1 genetic diversity remains challenging for viral load testing. Further studies are required in the same area to confirm the presence of HIV-1 strains that are not amplified with at least two different viral load assays.

Noninvasive follow-up of simian immunodeficiency virus infection in wild-living nonhabituated western lowland gorillas in Cameroon.

Simian immunodeficiency viruses infecting western lowland gorillas (SIVgor) are closely related to HIV-1 and are most likely the ancestors of HIV-1 groups O and P. At present, limited data are available on genetic diversity, transmission, viral evolution, and pathogenicity of SIVgor in its natural host. Between 2004 and 2011, 961 putative gorilla fecal samples were collected at the Campo Ma'an National Park, Cameroon. Among them, 16% cross-reacted with HIV-1 antibodies, corresponding to at least 34 infected gorillas. Combining host genotyping and field data, we identified four social groups composed of 7 to 15 individuals each, with SIV rates ranging from 13% to 29%. Eleven SIVgor-infected gorillas were sampled multiple times; two most likely seroconverted during the study period, showing that SIVgor continues to spread. Phylogenetic analysis of partial env and pol sequences revealed cocirculation of closely related and divergent strains among gorillas from the same social group, indicating SIVgor transmissions within and between groups. Parental links could be inferred for some gorillas infected with closely related strains, suggesting vertical transmission, but horizontal transmission by sexual or aggressive behavior was also suspected. Intrahost molecular evolution in one gorilla over a 5-year period showed viral adaptations characteristic of escape mutants, i.e., V1V2 loop elongation and an increased number of glycosylation sites. Here we show for the first time the feasibility of noninvasive monitoring of nonhabituated gorillas to study SIVgor infection over time at both the individual and population levels. This approach can also be applied more generally to study other pathogens in wildlife.

New STLV-3 strains and a divergent SIVmus strain identified in non-human primate bushmeat in Gabon.

BACKGROUND: Human retroviral infections such as Human Immunodeficiency Virus (HIV) or Human T-cell Lymphotropic Virus (HTLV) are the result of simian zoonotic transmissions through handling and butchering of Non-Human Primates (NHP) or by close contact with pet animals. Recent studies on retroviral infections in NHP bushmeat allowed for the identification of numerous Simian Immunodeficiency Viruses (SIV) and Simian T-cell Lymphotropic Viruses (STLV) to which humans are exposed. Nevertheless, today, data on simian retroviruses at the primate/hunter interface remain scarce. We conducted a pilot study on 63 blood and/or tissues samples derived from NHP bushmeat seized by the competent authorities in different locations across the country. RESULTS: SIV and STLV were detected by antibodies to HIV and HTLV antigens, and PCRs were performed on samples with an HIV or/and HTLV-like or indeterminate profile. Fourteen percent of the samples cross-reacted with HIV antigens and 44% with HTLV antigens. We reported STLV-1 infections in five of the seven species tested. STLV-3 infections, including a new STLV-3 subtype, STLV-1 and -3 co-infections, and triple SIV, STLV-1, STLV-3 infections were observed in red-capped mangabeys (C.torquatus). We confirmed SIV infections by PCR and sequence analyses in mandrills, red-capped mangabeys and showed that mustached monkeys in Gabon are infected with a new SIV strain basal to the SIVgsn/mus/mon lineage that did not fall into the previously described SIVmus lineages reported from the corresponding species in Cameroon. The same monkey (sub)species can thus be carrier of, at least, three distinct SIVs. Overall, the minimal prevalence observed for both STLV and SIV natural infections were 26.9% and 11.1% respectively. CONCLUSIONS: Overall, these data, obtained from a restricted sampling, highlight the need for further studies on simian retroviruses in sub-Saharan Africa to better understand their evolutionary history and to document SIV strains to which humans are exposed. We also show that within one species, a high genetic diversity may exist for SIVs and STLVs and observe a high genetic diversity in the SIVgsn/mon/mus lineage, ancestor of HIV-1/SIVcpz/SIVgor.

Human immunodeficiency viruses: SIV infection in wild gorillas.

Chimpanzees (Pan troglodytes troglodytes) from west central Africa are recognized as the reservoir of simian immunodeficiency viruses (SIVcpzPtt) that have crossed at least twice to humans: this resulted in the AIDS pandemic (from human immunodeficiency virus HIV-1 group M) in one instance and infection of just a few individuals in Cameroon (by HIV-1 group N) in another. A third HIV-1 lineage (group O) from west central Africa also falls within the SIVcpzPtt radiation, but the primate reservoir of this virus has not been identified. Here we report the discovery of HIV-1 group O-like viruses in wild gorillas.

Detection and genetic diversity of Mopeia virus in Mastomys natalensis from different habitats in the Limpopo National Park, Mozambique.

Mammarenaviruses have been a growing concern for public health in Africa since the 1970s when Lassa virus cases in humans were first described in west Africa. In southern Africa, a single outbreak of Lujo virus was reported to date in South Africa in 2008 with a case fatality rate of 80%. The natural reservoir of Lassa virus is Mastomys natalensis while for the Lujo virus the natural host has yet to be identified. Mopeia virus was described for the first time in M. natalensis in the central Mozambique in 1977 but few studies have been conducted in the region. In this study, rodents were trapped between March and November 2019in villages, croplands fields and mopane woodland forest. The aim was to assess the potential circulation and to evaluate the genetic diversity of mammarenaviruses in M. natalensis trapped in the Limpopo National Park and its buffer zone in Massingir district, Mozambique. A total of 534 M. natalensis were screened by RT-PCR and the overall proportion of positive individuals was 16.9%. No significant differences were detected between the sampled habitats (χ2 = 0.018; DF = 1; p = 0.893). The Mopeia virus (bootstrap value 91%) was the Mammarenavirus circulating in the study area sites, forming a specific sub-clade with eight different sub-clusters. We concluded that Mopeia virus circulates in all habitats investigated and it forms a different sub-clade to the one reported in central Mozambique in 1977.

Longitudinal Survey of Coronavirus Circulation and Diversity in Insectivorous Bat Colonies in Zimbabwe.

BACKGROUND: Studies have linked bats to outbreaks of viral diseases in human populations such as SARS-CoV-1 and MERS-CoV and the ongoing SARS-CoV-2 pandemic. METHODS: We carried out a longitudinal survey from August 2020 to July 2021 at two sites in Zimbabwe with bat-human interactions: Magweto cave and Chirundu farm. A total of 1732 and 1866 individual bat fecal samples were collected, respectively. Coronaviruses and bat species were amplified using PCR systems. RESULTS: Analysis of the coronavirus sequences revealed a high genetic diversity, and we identified different sub-viral groups in the Alphacoronavirus and Betacoronavirus genus. The established sub-viral groups fell within the described Alphacoronavirus sub-genera: Decacovirus, Duvinacovirus, Rhinacovirus, Setracovirus and Minunacovirus and for Betacoronavirus sub-genera: Sarbecoviruses, Merbecovirus and Hibecovirus. Our results showed an overall proportion for CoV positive PCR tests of 23.7% at Chirundu site and 16.5% and 38.9% at Magweto site for insectivorous bats and Macronycteris gigas, respectively. CONCLUSIONS: The higher risk of bat coronavirus exposure for humans was found in December to March in relation to higher viral shedding peaks of coronaviruses in the parturition, lactation and weaning months of the bat populations at both sites. We also highlight the need to further document viral infectious risk in human/domestic animal populations surrounding bat habitats in Zimbabwe.

Novel multiplexed HIV/simian immunodeficiency virus antibody detection assay.

Like most emerging infectious disease viruses, HIV is also of zoonotic origin. To assess the risk for cross-species transmission of simian immunodeficiency viruses (SIVs) from nonhuman primates to humans in the Democratic Republic of Congo, we collected 330 samples derived from nonhuman primate bushmeat at 3 remote forest sites. SIV prevalences were estimated by using a novel high-throughput assay that included 34 HIV and SIV antigens in a single well. Overall, 19% of nonhuman primate bushmeat was infected with SIVs, and new SIV lineages were identified. Highest SIV prevalences were seen in red-tailed guenons (25%) and Tshuapa red colobus monkeys (24%), representing the most common hunted primate species, thus increasing the likelihood for cross-species transmission. Additional studies are needed to determine whether other SIVs crossed the species barrier. With the newly developed assay, large-scale screening against many antigens is now easier and faster.

Molecular epidemiology of simian immunodeficiency virus infection in wild-living gorillas.

Chimpanzees and gorillas are the only nonhuman primates known to harbor viruses closely related to HIV-1. Phylogenetic analyses showed that gorillas acquired the simian immunodeficiency virus SIVgor from chimpanzees, and viruses from the SIVcpz/SIVgor lineage have been transmitted to humans on at least four occasions, leading to HIV-1 groups M, N, O, and P. To determine the geographic distribution, prevalence, and species association of SIVgor, we conducted a comprehensive molecular epidemiological survey of wild gorillas in Central Africa. Gorilla fecal samples were collected in the range of western lowland gorillas (n = 2,367) and eastern Grauer gorillas (n = 183) and tested for SIVgor antibodies and nucleic acids. SIVgor antibody-positive samples were identified at 2 sites in Cameroon, with no evidence of infection at 19 other sites, including 3 in the range of the Eastern gorillas. In Cameroon, based on DNA and microsatellite analyses of a subset of samples, we estimated the prevalence of SIVgor to be 1.6% (range, 0% to 4.6%), which is significantly lower than the prevalence of SIVcpzPtt in chimpanzees (5.9%; range, 0% to 32%). All newly identified SIVgor strains formed a monophyletic lineage within the SIVcpz radiation, closely related to HIV-1 groups O and P, and clustered according to their field site of origin. At one site, there was evidence for intergroup transmission and a high intragroup prevalence. These isolated hot spots of SIVgor-infected gorilla communities could serve as a source for human infection. The overall low prevalence and sporadic distribution of SIVgor could suggest a decline of SIVgor in wild populations, but it cannot be excluded that SIVgor is still more prevalent in other parts of the geographical range of gorillas.

No evidence for transmission of SIVwrc from western red colobus monkeys (Piliocolobus badius badius) to wild West African chimpanzees (Pan troglodytes verus) despite high exposure through hunting.

BACKGROUND: Simian Immunodeficiency Viruses (SIVs) are the precursors of Human Immunodeficiency Viruses (HIVs) which have led to the worldwide HIV/AIDS pandemic. By studying SIVs in wild primates we can better understand the circulation of these viruses in their natural hosts and habitat, and perhaps identify factors that influence susceptibility and transmission within and between various host species. We investigated the SIV status of wild West African chimpanzees (Pan troglodytes verus) which frequently hunt and consume the western red colobus monkey (Piliocolobus badius badius), a species known to be infected to a high percentage with its specific SIV strain (SIVwrc). RESULTS: Blood and plasma samples from 32 wild chimpanzees were tested with INNO-LIA HIV I/II Score kit to detect cross-reactive antibodies to HIV antigens. Twenty-three of the samples were also tested for antibodies to 43 specific SIV and HIV lineages, including SIVwrc. Tissue samples from all but two chimpanzees were tested for SIV by PCRs using generic SIV primers that detect all known primate lentiviruses as well as primers designed to specifically detect SIVwrc. Seventeen of the chimpanzees showed varying degrees of cross-reactivity to the HIV specific antigens in the INNO-LIA test; however no sample had antibodies to SIV or HIV strain- and lineage-specific antigens in the Luminex test. No SIV DNA was found in any of the samples. CONCLUSIONS: We could not detect any conclusive trace of SIV infection from the red colobus monkeys in the chimpanzees, despite high exposure to this virus through frequent hunting. The results of our study raise interesting questions regarding the host-parasite relationship of SIVwrc and wild chimpanzees in their natural habitat.

Favipiravir Inhibits Mayaro Virus Infection in Mice.

Mayaro virus (MAYV) is an emergent alphavirus that causes MAYV fever. It is often associated with debilitating symptoms, particularly arthralgia and myalgia. MAYV infection is becoming a considerable health issue that, unfortunately, lacks a specific antiviral treatment. Favipiravir, a broad-spectrum antiviral drug, has recently been shown to exert anti-MAYV activity in vitro. In the present study, the potential of Favipiravir to inhibit MAYV replication in an in vivo model was evaluated. Immunocompetent mice were orally administrated 300 mg/kg/dose of Favipiravir at pre-, concurrent-, or post-MAYV infection. The results showed a significant reduction in infectious viral particles and viral RNA transcripts in the tissues and blood of the pre- and concurrently treated infected mice. A significant reduction in the presence of both viral RNA transcript and infectious viral particles in the tissue and blood of pre- and concurrently treated infected mice was observed. By contrast, Favipiravir treatment post-MAYV infection did not result in a reduction in viral replication. Interestingly, Favipiravir strongly decreased the blood levels of the liver disease markers aspartate- and alanine aminotransferase in the pre- and concurrently treated MAYV-infected mice. Taken together, these results suggest that Favipiravir is a potent antiviral drug when administered in a timely manner.

Mayaro Virus Infects Human Brain Cells and Induces a Potent Antiviral Response in Human Astrocytes.

Mayaro virus (MAYV) and chikungunya virus (CHIKV) are known for their arthrotropism, but accumulating evidence shows that CHIKV infections are occasionally associated with serious neurological complications. However, little is known about the capacity of MAYV to invade the central nervous system (CNS). We show that human neural progenitors (hNPCs), pericytes and astrocytes are susceptible to MAYV infection, resulting in the production of infectious viral particles. In primary astrocytes, MAYV, and to a lesser extent CHIKV, elicited a strong antiviral response, as demonstrated by an increased expression of several interferon-stimulated genes, including ISG15, MX1 and OAS2. Infection with either virus led to an enhanced expression of inflammatory chemokines, such as CCL5, CXCL10 and CXCL11, whereas MAYV induced higher levels of IL-6, IL-12 and IL-15 in these cells. Moreover, MAYV was more susceptible than CHIKV to the antiviral effects of both type I and type II interferons. Taken together, this study shows that although MAYV and CHIKV are phylogenetically related, they induce different types of antiviral responses in astrocytes. This work is the first to evaluate the potential neurotropism of MAYV and shows that brain cells and particularly astrocytes and hNPCs are permissive to MAYV, which, consequently, could lead to MAYV-induced neuropathology.

Full-length genome sequence of a simian immunodeficiency virus (SIV) infecting a captive agile mangabey (Cercocebus agilis) is closely related to SIVrcm infecting wild red-capped mangabeys (Cercocebus torquatus) in Cameroon.

Simian immunodeficiency viruses (SIVs) are lentiviruses that infect an extensive number of wild African primate species. Here we describe for the first time SIV infection in a captive agile mangabey (Cercocebus agilis) from Cameroon. Phylogenetic analysis of the full-length genome sequence of SIVagi-00CM312 showed that this novel virus fell into the SIVrcm lineage and was most closely related to a newly characterized SIVrcm strain (SIVrcm-02CM8081) from a wild-caught red-capped mangabey (Cercocebus torquatus) from Cameroon. In contrast to red-capped mangabeys, no 24 bp deletion in CCR5 has been observed in the agile mangabey. Further studies on wild agile mangabeys are needed to determine whether agile and red-capped mangabeys are naturally infected with the same SIV lineage, or whether this agile mangabey became infected with an SIVrcm strain in captivity. However, our study shows that agile mangabeys are susceptible to SIV infection.